Paula Viñas
José de Felippe Junior

Existem muitas espécies de plantas que inibem a proliferação celular maligna, aumentam a apoptose, interferem na angiogenese tumoral , e assim auxiliam no tratamento do câncer.

Devemos ter muito cuidado quando usamos as plantas em conjunto com a quimioterapia ou radioterapia. A maioria das plantas possuem alto poder antioxidante e realmente protegem os pacientes dos efeitos colaterais da quimiterapia e radioterapia , porém diminuem a eficácia destas modalidades terapêuticas. A explicação é que tanto a radioterapia como a quimioterapia utilizam os radicais livres para oxidar e matar as células malignas e assim os antioxidantes seja na forma de planta ou de vitaminas antioxidantes ( vitamina E , vitamina C ) atrapalham o tratamento convencional do câncer. ( vide “ Biblioteca de Câncer” neste site)

Abacaxi

Modulation of pulmonary metastasis (Lewis lung carcinoma) by bromelain, an extract of the pineapple stem (Ananas comosus)
Cancer Invest. 1988;6(2):241-2.

Inhibition of tumour growth in vitro by bromelain, an extract of the pineapple plant (Ananas comosus).
Planta Med. 1985 Dec;(6):538-9.
Taussig SJ, Szekerczes J, Batkin S.

Alecrin de Jardim

Carnosic acid inhibits proliferation and augments differentiation of human leukemic cells induced by 1,25-dihydroxyvitamin D3 and retinoic acid.
Nutr Cancer. 2001;41(1-2):135-44.
Steiner M, Priel I, Giat J, Levy J, Sharoni Y, Danilenko M.
Department of Clinical Biochemistry, Faculty of Health Sciences, Ben-Gurion University of the Negev and Soroka Medical Center of Kupat Holim, Beer-Sheva 84 105, Israel. misha@bgumail.bgu.ac.il
Carnosic acid, the polyphenolic diterpene derived from rosemary, is a strong dietary antioxidant that exhibits antimutagenic properties in bacteria and anticarcinogenic activity in various cell and animal models. In the present study, we show that carnosic acid (2.5-10 microM) inhibits proliferation of HL-60 and U937 human myeloid leukemia cells (half-maximal inhibitory concentration = 6-7 microM) without induction of apoptotic or necrotic cell death. Growth arrest occurred concomitantly with a transient cell cycle block in the G1 phase, which was accompanied by an increase in the immunodetectable levels of the universal cyclin-dependent kinase inhibitors p21WAFI and p27Kipl. Carnosic acid caused only a marginal induction of differentiation, as monitored by the capacity to generate superoxide radicals and the expression of cell surface antigens (CD11b and CD14) and receptors for the chemotactic peptide N-formyl-L-methionyl-L-leucyl-L-phenylalanine. However, at low concentrations, this polyphenol substantially augmented (100- to 1,000-fold) the differentiating effects of 1,25-dihydroxyvitamin D3 and all-trans retinoic acid. Furthermore, such combinations of carnosic acid and any of these differentiation inducers synergistically inhibited proliferation and cell cycle progression. These results indicate that carnosic acid is capable of antiproliferative action in leukemic cells and can cooperate with other natural anticancer compounds in growth-inhibitory and differentiating effects.

Inhibition of skin tumorigenesis by rosemary and its constituents carnosol and ursolic acid.
Cancer Res. 1994 Feb 1;54(3):701-8.
Huang MT, Ho CT, Wang ZY, Ferraro T, Lou YR, Stauber K, Ma W, Georgiadis C, Laskin JD, Conney AH.
Department of Chemical Biology and Pharmacognosy, College of Pharmacy, Rutgers
A methanol extract of the leaves of the plant Rosmarinus officinalis L. (rosemary) was evaluated for its effects on tumor initiation and promotion in mouse skin. Application of rosemary to mouse skin inhibited the covalent binding of benzo(a)pyrene [B(a)P] to epidermal DNA and inhibited tumor initiation by B(a)P and 7,12-dimethylbenz[a]anthracene (DMBA). Topical application of 20 nmol B(a)P to the backs of mice once weekly for 10 weeks, followed 1 week later by promotion with 15 nmol 12-O-tetradecanoylphorbol-13-acetate (TPA) twice weekly for 21 weeks, resulted in the formation of 7.1 tumors per mouse. In a parallel group of animals that were treated topically with 1.2 or 3.6 mg of rosemary 5 min prior to each application of B(a)P, the number of tumors per mouse was decreased by 54 or 64%, respectively. Application of rosemary to mouse skin also inhibited TPA-induced ornithine decarboxylase activity, TPA-induced inflammation, arachidonic acid-induced inflammation, TPA-induced hyperplasia, and TPA-induced tumor promotion. Mice initiated with 200 nmol DMBA and promoted with 5 nmol TPA twice weekly for 19 weeks developed an average of 17.2 skin tumors per mouse. Treatment of the DMBA-initiated mice with 0.4, 1.2, or 3.6 mg of rosemary together with 5 nmol TPA twice weekly for 19 weeks inhibited the number of TPA-induced skin tumors per mouse by 40, 68, or 99%, respectively. Topical application of carnosol or ursolic acid isolated from rosemary inhibited TPA-induced ear inflammation, ornithine decarboxylase activity, and tumor promotion. Topical application of 1, 3, or 10 mumol carnosol together with 5 nmol TPA twice weekly for 20 weeks to the backs of mice previously initiated with DMBA inhibited the number of skin tumors per mouse by 38, 63, or 78%, respectively. Topical application of 0.1, 0.3, 1, or 2 mumol ursolic acid together with 5 nmol TPA twice weekly for 20 weeks to DMBA-initiated mice inhibited the number of tumors per mouse by 45-61%.

Inhibition of 7,12-dimethylbenz[a]anthracene (DMBA)-induced mammary tumorigenesis and of in vivo formation of mammary DMBA-DNA adducts by rosemary extract.
Cancer Lett. 1991 Nov;60(2):169-75.
Singletary KW, Nelshoppen JM.
Division of Foods and Nutrition, University of Illinois, Urbana-Champaign.
The effect of dietary intake of an extract of the spice plant Rosmarinus officinalis L. on 7,12-dimethylbenz[a]anthracene (DMBA)-induced mammary tumorigenesis and on the in vivo formation of mammary DMBA-DNA adducts was evaluated. Supplementation of a semi-purified diet with 1.0% (by wt.) rosemary extract resulted in a significant (47%) decrease in mammary tumor incidence compared to controls. In subsequent studies, dietary supplementation with 0.5% and 1.0% rosemary extract inhibited total in vivo binding of DMBA to mammary epithelial cell DNA by an average of 42%. This decrease in total binding was not due to a uniform decrease in the formation of all mammary DMBA-DNA adducts. The formation of two major adducts derived from the anti-diastereomer of DMBA and bound to deoxyguanosine (anti-dGuo) was significantly decreased at both dietary rosemary concentrations. The formation of the syn-dGuo adduct also was inhibited, whereas formation of the syn-dAdo adduct was unaffected by consumption of the rosemary extract. These studies suggest that use of rosemary extract and its individual antioxidative constituents as chemopreventative agents for experimental mammary tumorigenesis warrant further investigation.

Panax Ginseng

A case-control study of ginseng intake and cancer.

Int J Epidemiol;19(4):871-6, 1990 Dec. Yun TK; Choi SY

Laboratory of Cancer Pathology, Korea Cancer Center Hospital, Seoul.

Resumo: The effect of ginseng consumption on the risk of cancer was investigated by interviewing 905 pairs of cases and controls matched by age, sex, and date of admission to the Korea Cancer Center Hospital, Seoul, Korea. Of the 905 cases 562 (62%) had a history of ginseng intake compared to 674 of the 905 controls (75%) a statistically significant difference (p less than 0.01). The odds ratio (OR) of cancer in relation to ginseng intake was 0.56 (95% confidence interval (CI), 0.45-0.69). Ginseng extract and powder were shown to be more effective than fresh sliced ginseng, the juice, or tea in reducing the OR. Odds ratios for decreasing levels of ginseng intake were 1.00, 0.58, 0.43 and 0.25 for males and 1.00, 0.81, 0.56 and 0.52 for females. A trend test showed a significant decrease in proportion of cancer cases with increasing frequency of intake for males (p less than 10(-5)) as well as for females (p less than 0.05). Chi-square homogeneity tests also confirmed significant differences between cases and controls for both sexes (p less than 10(-3)). The reliability of recall for ginseng use was assessed by interviewing 180 randomly-selected subjects twice using the same questionnaire. The overall agreement in reported ginseng use between the two interviews was 0.85, and the Kappa value was 0.71 (p less than 0.01). These results strongly support the hypothesis of preventive effects of ginseng on cancer suggested by earlier animal studies.

A new medical trend in China.

Am J Chin Med;3(3):213-21, 1975 Jul. Li CP

Resumo: Chinese biomedical scientists are now developing a new approach to medicine by combining traditional Chinese medicine and Western biomedical science. This is the current medical trend in China. Some significant results have already been achieved. For instance, in treating fractures the traditional dexterity in coaxing broken ends of bones into alignment has been successfully adopted, and x-ray has been used to check whether there was accurate bone union. Heart diseases are treated with Western drugs in combination with Chinese herbal medicine, and the results are encouraging. Ancient theories such as Fu Chen Pei Ben (to strengthen the patient's vitality) are applied, for instance, in cancer therapy, i.e., to stimulate the patient's appetite and to improve his general condition with herbs while being treated with Western anti-cancer remedies. However, the Chinese admit that this process has only just begun.

Cancer prevention and therapeutics: Panax ginseng.

Altern Med Rev;9(3):259-74, 2004 Sep. Helms S

Resumo: Panax ginseng has been used as a medicinal plant in China for thousands of years. Current use in Western countries has been diverse, with focused research on cancer therapeutics. P. ginseng apparently mitigates cancer through anti-inflammatory, antioxidant, and apoptotic mechanisms to influence gene expression. Additional mechanisms of investigation include influence on neurotransmission and immunosurveillance. Low toxicity and positive studies in concomitant use with other chemotherapeutic agents is promising. Although there is no conclusive evidence of P. ginseng curing cancer, research has continually found tumor inhibition, especially in the promotion and progression phases.

Immune system effects of echinacea, ginseng, and astragalus: a review.

Integr Cancer Ther;2(3):247-67, 2003 Sep. Block KI; Mead MN

Resumo: Traditional herbal medicine provides several remedies for strengthening the body's resistance to illness through effects on immune system components. This review article examines 3 popular herbal immune stimulants that are often of interest to cancer patients. Echinacea, a native of North America, is widely used to prevent, or provide early treatment for, colds. Preclinical studies lend biological plausibility to the idea that echinacea works through immune mechanisms. Numerous clinical trials have been carried out on echinacea preparations: it appears that the extracts shorten the duration and severity of colds and other upper respiratory infections (URIs) when given as soon as symptoms become evident. However, trials of long-term use of echinacea as a preventive have not shown positive results. Ginseng has been studied in some depth as an antifatigue agent, but studies of immune mechanisms have not proceeded so far. Preclinical evidence shows some immune-stimulating activity. There have been several clinical trials in a variety of different diseases. Astragalus is the least-studied agent. There are some preclinical trials that show intriguing immune activity. The herbs discussed appear to have satisfactory safety profiles. Cancer patients may wish to use these botanicals to inhibit tumor growth or to boost resistance to infections. However, passive immunotherapy with herbs, with no mechanism to expose tumor antigens, is unlikely to be effective in inhibiting tumor growth. Although the margin of safety for these herbs is large, more research is needed to demonstrate the clear value of using herbs to improve resistance to infections.

Panax ginseng: a role in cancer therapy?

Integr Cancer Ther;2(1):13-33, 2003 Mar Chang YS; Seo EK; Gyllenhaal C; Block KI. School of Pharmacy, China Medical College, Taichung, Taiwan, Republic of China.

Resumo: Panax ginseng is a plant that has been used in traditional medicine in China for thousands of years. It is used as a general tonic or adaptogen with chronically ill patients and is frequently featured in traditional medicine prescriptions from China, Japan, and Korea used by cancer patients. The putative active compounds are the ginsenosides, of which there are more than two dozen. These compounds are found in both Panax ginseng and in other Panax species that are used in herbal medicine. Analysis of ginsenosides is being used in developing quality control assessments for ginseng, which has frequently been adulterated due to its high cost; many currently available standardized extracts do appear to contain the amounts of ginsenosides listed on package labeling. The toxicity of ginseng appears to be low: some of the reports of toxic episodes of ginseng may actually pertain to other components of multicomponent preparations. Very low incidence of toxicity has been observed in ginseng clinical trials using well-characterized preparations. Numerous pharmacological activities of ginseng and the ginsenosides have been explored: the authors review here the activities relating to cancer. Immune system modulation, antistress activities, and antihyperglycemic activities are among the most notable features of ginseng noted in laboratory and clinical analyses. Much testing has been done in humans to explore ginseng's purported antifatigue properties, but this area remains controversial. A number of investigations point to antitumor properties and other pharmacological activities related to cancer, but no trials have yet confirmed a clinically significant anticancer activity. Cancer patients may empirically find ginseng to be useful when they are fatigued, although clinical trials should be conducted to confirm its benefits.

Panax ginseng--a non-organ-specific cancer preventive?

Lancet Oncol;2(1):49-55, 2001 Jan. Yun TK

Resumo: For the past 50 years, the main weapons in the war against cancer have been early detection and surgical removal, radiotherapy, chemotherapy, and attempts to develop gene therapy. However, the results so far are less than ideal. One strategy now is to switch from therapeutic approaches to prevention of cancer by improving lifestyle and by identifying effective natural products as chemopreventive agents. One promising candidate with cancer-preventive effects that are not specific to any organ is Panax ginseng C A Meyer, a herb with a long medicinal history. Its protective influence against cancer has been shown by extensive preclinical and epidemiological studies, but these effects need to be carefully investigated by scientific clinical trials focusing on the major cancer killers stomach, lung, liver, and colorectal cancer.

Chemistry and cancer preventing activities of ginseng saponins and some related triterpenoid compounds.

J Korean Med Sci;16 Suppl:S28-37, 2001 Dec Shibata S.

Shibata Laboratory of Natural Medicinal Materials c/o Minophagen Pharmaceutical Co. Ltd., Tokyo, Japan

País de publicação: Korea (South)

Resumo: More than 25 dammarane-type tetracyclic triterpenoid saponins have been isolated from ginseng, the root and rhizome of Panax ginseng C.A. Meyer (Araliaceae). The genuine sapogenins of those saponins, 20(S)-protopanaxa-diol and -triol, were identified as 20(S) 12beta-hydroxy-and 20(S) 6alpha,12beta-dihydroxy-dammarenediol-II, respectively. There are two types of preparations from ginseng: white ginseng prepared by drying after peelling off and red ginseng prepared by steaming and drying. Some partly deglycosylated saponins such as ginsenoside Rh-1, Rh-2, and Rg-3 are obtained from red ginseng as artifacts produced during steaming. Several workers studied the metabolic transformation by human intestinal bacteria after oral administration of ginsenoside Rb-1 and Rb-2 and found that the stepwise deglyco-sylation yielded compound K and finally 20(S)-protopanaxadiol. Ginsenoside Rg-1 was converted into 20(S)-protopanaxatriol via ginsenoside Rh-1. Yun et al. in Korea conducted the epidemiological case-control studies of ginseng and suggested its cancer preventing activities. Kitagawa et al. demonstrated in vitro that ginsenosides, especially 20(R)-ginsenoside Rg-3, specifically inhibited cancer cell invasion and metastasis. Azuma et al. found that ginsenoside Rb-2 inhibited tumor angiogenesis, and Kikuchi et al. reported that ginsenoside Rh-2 inhibited the human ovarian cancer growth in nude mice. Recently, ginsenoside Rg-3 was produced as an anti-angiogenic anti-cancer drug in China. The aforementioned reports suggest that less glycosylated protopanaxadiol derivatives are effective in cancer prevention. Apart from Ginseng tetracyclic triterpenoid saponins, some oleanane-type pentacyclic triterpenoid compounds showed the anti-carcinogenic activity in the two-stage anti-cancer-promotion experiments in vitro and in vivo.

Epidemiological study on cancer prevention by ginseng: are all kinds of cancers preventable by ginseng?

J Korean Med Sci;16 Suppl:S19-27, 2001 Dec. Yun TK; Choi SY; Yun HY

País de publicação: Korea (South) Laboratory of Experimental Pathology, Korea Cancer Center Hospital, Seoul, Korea.

Resumo: In the light of experimental results, two case-control studies and one cohort study in a population of ginseng cultivation area were conducted to confirm whether ginseng has any anticarcinogenic effect on human cancers. All participants were interviewed using a standardised questionnaire to obtain the information on demographics, cigarette smoking, alcohol consumption and ginseng intake. In 905 pairs case-control study, 62% had a history of ginseng intake compared to 75% of the controls, a statistically significant difference (p<0.01). The odds ratio (OR) for cancer in relation to ginseng intake was 0.56. In extended case-control study with 1987 pairs, the ORs for cancer were 0.37 in fresh ginseng extract users, 0.57 in white ginseng extract users, 0.30 in white ginseng extract users, 0.30 in white ginseng powder users, and 0.20 in red ginseng users. Those who took fresh ginseng slices, fresh ginseng juice, and white ginseng tea, however, did not show decrease in the risk. Overall, the risk decreased as the frequency and duration of ginseng intake increased. With respect to the site of cancer, the ORs for cancers of the lip, oral cavity, pharynx, esophagus, stomach, colorectum, liver, pancreas, larynx, lung and ovary were significantly reduced by ginseng intake. Smokers with ginseng intake showed lower ORs for cancers of lung, lip, oral cavity and pharynx and liver than those without ginseng intake. In 5 yr follow- up cohort study conducted in the ginseng cultivation area, Kangwha-eup, ginseng intakers had significantly lower risk than non-intakers. As for the type of ginseng, cancer risk significantly decreased among intakers of fresh ginseng extract, alone or together with other ginseng preparations. Among 24 red ginseng intakers, no cancer death occurred during the follow-up period. The risk for stomach and lung cancers was significantly reduced by ginseng intake, showing a statistically significant dose-response relationship in each follow-up year. In conclusion, Panax ginseng C.A. Meyer has been established as non-organ specific cancer preventive, having dose response relationship. These results warrant that ginseng extracts and its synthetic derivatives should be examined for their preventive effect on various types of human cancers.

Asian studies of cancer chemoprevention: latest clinical results.

:Eur J Cancer;36(10):1303-9, 2000 Jun. Kakizoe T

National Cancer Center Hospital, Tsukiji 5-1-1, Chuo-Ku, 104-0045, Tokyo, Japan. tkakizoe@ncc.go.jp

Resumo: Chemoprevention trials in Asia, including those already completed and those now ongoing, are reviewed. Information was mainly collected from Japan, Korea and China. Each country features its own characteristics. Cancer chemoprevention trials targeting, from various aspects, hepatocellular carcinoma, gastric cancer and colon cancer have been, and are now being, conducted in Japan. Japan also has a long history of basic carcinogenesis research and carcinogenic research using animal experiments. In Korea, ginseng is the main focus of studies of chemopreventive agents. A large body of information has been collected and prospective studies are also ongoing. In China, the Linxian study, a cooperative study participated in by China and the NCI of the USA, is well known and the results impressive. However, we must exercise caution because, for example, the population of Linxian are chronically deficient in multiple vitamins and trace minerals. This situation may, therefore, differ from that observed in other countries. In any event, chemoprevention studies will be popular from an economical point of view even in Asia because cancer is becoming the number one cause of death in these countries.

The cancer-preventive potential of Panax ginseng: a review of human and experimental evidence.

Cancer Causes Control;11(6):565-76, 2000 Jul. Shin HR; Kim JY; Yun TK; Morgan G; Vainio H Department of Preventive Medicine, College of Medicine, Dong-A University, Pusan, Korea.

Resumo: OBJECTIVE: We have reviewed the potential cancer-preventive and other relevant properties of Panax ginseng C. A. Meyer, which has been traditionally used as a natural tonic in Oriental countries. DATA IDENTIFICATION AND STUDY SELECTION: Publications on Panax ginseng and its relation to cancer were obtained from the Medline database (1983-1998) and by checking reference lists to find earlier reports. The reports cover experimental models and human studies on cancer-preventive activity, carcinogenicity and other beneficial or adverse effects. In addition, possible mechanisms of chemoprevention by ginseng were considered. RESULTS: Published results from a cohort and two case-control studies in Korea suggest that the intake of ginseng may reduce the risk of several types of cancer. When ginseng was tested in animal models, a reduction in cancer incidence and multiplicity at various sites was noted. Panax ginseng and its chemical constituents have been tested for their inhibiting effect on putative carcinogenesis mechanisms (e.g., cell proliferation and apoptosis, immunosurveillance, angiogenesis); in most experiments inhibitory effects were found. CONCLUSION: While Panax ginseng C. A. Meyer has shown cancer-preventive effects both in experimental models and in epidemiological studies, the evidence is currently not conclusive as to its cancer-preventive activity in humans. The available evidence warrants further research into the possible role of ginseng in the prevention of human cancer and carcinogenesis.

Panax (ginseng)--panacea or placebo? Molecular and cellular basis of its pharmacological activity.

Ann Acad Med Singapore;29(1):42-6, 2000 Jan. Ong YC; Yong EL Department of Obstetrics & Gynaecology, National University of Singapore, Singapore.

País de publicação: SINGAPORE

Resumo: INTRODUCTION: The use of ethnobotanical drugs amongst Asians as complementary medicine is prevalent and is also gaining increasing popularity in the West. The most well-known herb traditionally used as a drug is the root of the ginseng species. There are many traditional and anecdotal claims to the therapeutic properties of ginseng. In recent years, there have been systematic efforts to analyse the bioactivities of ginseng saponins. METHODS: A comprehensive review of published literature covering molecular and cellular research as well as animal and human studies on ginseng and its derivatives. RESULTS AND CONCLUSION: Current published data would serve as a framework to understand the pharmacology of ginseng in its entirety, from its molecular action to actual therapeutic effects observed in human use. A new paradigm is emerging whereby the pharmacological effects of traditional herbs such as ginseng can be understood in the light of their polyvalent actions as demonstrated by ginseng saponins with their positive anti-mutagenic, anti-cancer, anti-inflammatory, anti-diabetes and neurovascular effects. With increasing understanding, evidence-based incorporation of traditional herbs as complementary medicine into mainstream medical science can be achieved in the near future.

Update from Asia. Asian studies on cancer chemoprevention.

Ann N Y Acad Sci;889:157-92, 1999. Yun TK

Resumo: In Asia, nontoxic dietary products are considered desirable primary prevention vehicles for conquering cancer. As early as 1978, investigators in Korea carried out extensive long-term anticarcinogenicity experiments using the mouse lung tumor model and observed an anticarcinogenic effect of Panax ginseng C.A. Meyer extract in 1980. The results showed that natural products can provide hope for human cancer prevention. A newly established nine-week medium-term model using mouse lung tumors (Yun's model) could confirm the anticarcinogenicity of ginseng that varies according to its type and age. Subsequently, the ginseng was shown by epidemiological studies to be a nonorgan-specific cancer preventive agent associated with a dose-response relationship. The anticarcinogenic effects of vegetarian foods common at every dining table in Korea and some synthetics were also studied using Yun's nine-week model. In brief, ascorbic acid, soybean lecithin, capsaicin, biochanin A, Ganoderma lucidum, caffeine, and a novel synthetic 2-(allylthio)pyrazine decrease the incidence of mouse lung tumors, whereas fresh ginseng (4 years old), carrot, spinach, Sesamum indicum, beta-carotene, and 13-cis retinoic acid do not. This result regarding beta-carotene is consistent with the ineffective findings of the ATBC trial, the CARET trial, and the Physicians' Health Study. In 1983, a cancer chemoprevention study group was first established in Japan. Subsequently, (-)-epigallocatechin gallate, cryptoporic acid E, and sarcophytol A from natural products, and synthetic acyclic retinoid and canventol were shown to be anticarcinogenic or chemopreventive in human subjects. Despite the frequent consumption of tea wordwide as a beverage and current experimental evidence of anticarcinogenesis, including controversial results of epidemiological studies, more systematic clinical trials for confirmation of preventive activity of tea against cancer are needed. Placebo-controlled intervention trials of dietary fiber are under study in Japan. In the past decade, new triterpenoids were isolated from various natural sources, and its biological activities were investigated in Asia. In the late 1970s a comprehensive chemoprevention program was established at the Institute of Materia Medica, Chinese Academy of Medical Sciences. Since then, many retinoid compounds have been synthesized and screened in the search for chemopreventive cancer agents. The National Cancer Institute (USA) and China are jointly engaged in the two-nutrition intervention in Linxian, China. The results of joint study of the general population and of dysplasia in China should stimulate further research to clarify the potential benefits of micronutrient supplements. We need to clarify if there is a connection between the lower rates of cancer mortality in Korea and the frequent consumption of anticarcinogenic vegetables or traditional foods, including ginseng and Ganoderma lucidum. The constituents of the nontoxic stable dietary products promise to be the future hope for conquering cancers in the coming years.

Non-organ specific cancer prevention of ginseng: a prospective study in Korea.

Int J Epidemiol;27(3):359-64, 1998 Jun. Yun TK; Choi SY

Laboratory of Experimental Pathology, Korea Cancer Center Hospital, Seoul.

Resumo: BACKGROUND: A number of studies have reported that increased consumption of natural products reduced the risk of cancer. Our previous case-control studies have shown a significant reduction in the risk of cancer development among those who regularly consumed ginseng. We conducted a prospective cohort study to evaluate the preventive effect of ginseng against cancer on a population residing in a ginseng cultivation area on the basis of the result of case-control studies. METHODS: This study was conducted in Kangwha-eup from August 1987 to December 1992. We studied 4634 people over 40 years old who completed a questionnaire on ginseng intake. In an attempt to obtain detailed information about ginseng intake, we asked them to specify their age at initial intake, their frequency and duration of ginseng intake, the kind of ginseng, etc. Multiple logistic regression was used to estimate relative risks (RR) when controlling simultaneously for covariates. RESULTS: Ginseng consumers had a decreased risk (RR = 0.40, 95% confidence interval [CI] : 0.28-0.56) compared with non-consumers. On the type of ginseng, the RR was 0.31 (95% CI: 0.13-0.74) for fresh ginseng extract consumers and 0.34 (95% CI: 0.20-0.53) for consumers of multiple combinations. There was no cancer death among 24 red ginseng consumers. There was a decreased risk with a rise in the frequency of ginseng intake, showing a dose-response relationship. The RR of ginseng consumers were 0.33 (95% CI: 0.18-0.57) in gastric cancer and 0.30 (95% CI : 0.14-0.65) in lung cancer. Among ginseng preparations, fresh ginseng extract consumers were significantly associated with a decreased risk of gastric cancer (RR = 0.33, 95% CI: 0.12-0.88). CONCLUSIONS: These results strongly suggest that Panax ginseng C.A. Meyer has non-organ specific preventive effect against cancer, providing support for the previous case-control studies.

Preventive effect of ginseng intake against various human cancers: a case-control study on 1987 pairs.

Cancer Epidemiol Biomarkers Prev;4(4):401-8, 1995 Jun. Yun TK; Choi SY

Laboratory of Cancer Pathology, Korea Cancer Center Hospital, Seoul.

Resumo: This study presents the risk of various cancers in relation to ginseng intake based on the data from a case-control study conducted in the Korea Cancer Center Hospital. Ginseng intakers had a decreased risk [odds ratio = 0.50, 95% confidence interval (CI) = 0.44-0.58] for cancer compared with nonintakers. On the type of ginseng, the odds ratios for cancer were 0.37 (95% CI = 0.29-0.46) for fresh ginseng extract intakers, 0.57 (95% CI = 0.48-0.68) for white ginseng extract intakers, 0.30 (95% CI = 0.22-0.41) for white ginseng powder intakers, and 0.20 (95% CI = 0.08-0.50) for red ginseng intakers. Intakers of fresh ginseng slice, fresh ginseng juice, and white ginseng tea, however, showed no decreasing risk. There was a decrease in risk with the rising frequency and duration of ginseng intake, showing a dose-response relationship. On the site of cancer, the odds ratios were 0.47 for cancer of the lip, oral cavity, and pharynx; 0.20 for esophageal cancer; 0.36 for stomach cancer; 0.42 for colorectal cancer; 0.48 for liver cancer; 0.22 for pancreatic cancer; 0.18 for laryngeal cancer; 0.55 for lung cancer; and 0.15 for ovarian cancer. In cancers of the female breast, uterine cervix, urinary bladder, and thyroid gland, however, there was no association with ginseng intake. In cancers of the lung, lip, oral cavity and pharynx, and liver, smokers with ginseng intake showed decreased odds ratios compared with smokers without ginseng intake. These findings support the view that ginseng intakers had a decreased risk for most cancers compared with nonintakers.

Alho

The potential application of Allium sativum (garlic) for the treatment of bladder cancer.
Urol Clin North Am. 2000 Feb;27(1):157-62, xi.
Lamm DL, Riggs DR.
Department of Urology, Robert C. Byrd Health Science Center, West Virginia University, Morgantown, USA. Dlamm@wvuhsc1.hsc.wvu.edu

Additional studies are needed to identify the active ingredients in Allium Sativum (garlic) that are responsible for the observed antitumor activity and immune stimulation. Garlic seems to detoxify chemical carcinogens and prevent carcinogenesis and can also directly inhibit the growth of cancer cells. Current data suggest that low molecular weight sulfur compounds and protein F4 have immune-stimulation properties. Garlic is reported to stimulate immunity, including macrophage activity, natural killer and killer cells, and LAK cells, and to increase the production of IL-2, TNF, and interferon-gamma. These cytokines are associated with the beneficial Th1 antitumor response, which is characteristic of effective cancer immunotherapies. As is true of BCG, garlic stimulates the proliferation of macrophages and lymphocytes and protects against the suppression of immunity by chemotherapy and ultraviolet radiation. Garlic is clearly not a panacea for cancer, but its broad range of beneficial effects are worthy of serious consideration in clinical trials for the prevention and treatment of cancer.

Modulation of programmed cell death by medicinal plants.
Cell Mol Biol (Noisy-le-grand). 2000 Feb;46(1):199-214.
Thatte U, Bagadey S, Dahanukar S.
Department of Pharmacology and Therapeutics, Seth GS Medical College, Parel, Mumbai, India. kemarc@vsnl.com

Programmed cell death (apoptosis), a form of cell death, described by Kerr and Wyllie some 20 years ago, has generated considerable interest in recent years. The mechanisms by which this mode of cell death (seen both in animal and plant cells), takes place have been examined in detail. Extracellular signals and intracellular events have been elaborated. Of interest to the clinician, is the concentrated effort to study pharmacological modulation of programmed cell death. The attempt to influence the natural phenomenon of programmed cell death stems from the fact that it is reduced (like in cancer) or increased (like in neurodegenerative diseases) in several clinical situations. Thus, chemicals that can modify programmed cell death are likely to be potentially useful drugs. From foxglove, which gave digitalis to the Pacific Yew from which came taxol, plants have been a source of research material for useful drugs. Recently, a variety of plant extracts have been investigated for their ability to influence the apoptotic process. This article discusses some of the interesting data. The ability of plants to influence programmed cell death in cancerous cells in an attempt to arrest their proliferation has been the topic of much research. Various cell-lines like HL60, human hepatocellular carcinoma cell line (KIM-1), a cholangiocarcinoma cell-line (KMC-1), B-cell hybridomas, U937 a monocytic cell-line, HeLa cells, human lymphoid leukemia (MOLT-4B) cells and K562 cells have been studied. The agents found to induce programmed cell death (measured either morphologically or flow cytometrically) included extracts of plants like mistletoe and Semicarpus anacardium. Isolated compounds like bryonolic acid (from Trichosanthes kirilowii var. Japonica, crocin (from saffron) and allicin (from Allium sativum) have also been found to induce programmed cell death and therefore arrest proliferation. Even Chinese herbal medicine "Sho-saiko-to" induces programmed cell death in selected cancerous cell lines. Of considerable interest is the finding that Panax ginseng prevents irradiation-induced programmed cell death in hair follicles, suggesting important therapeutic implications. Nutraceuticals (dietary plants) like soya bean, garlic, ginger, green tea, etc. which have been suggested, in epidemiological studies, to reduce the incidence of cancer may do so by inducing programmed cell death. Soy bean extracts have been shown to prevent development of diseases like polycystic kidneys, while Artemisia asiatica attenuates cerulein-induced pancreatitis in rats. Interestingly enough, a number of food items as well as herbal medicines have been reported to produce toxic effects by inducing programmed cell death. For example, programmed cell death in isolated rat hepatocytes has been implicated in the hepatitis induced by a herbal medicine containing diterpinoids from germander. Other studies suggest that rapid progression of the betel- and tobacco-related oral squamous cell carcinomas may be associated with a simultaneous involvement of p53 and c-myc leading to inhibition of programmed cell death. Several mechanisms have been identified to underlie the modulation of programmed cell death by plants including endonuclease activation, induction of p53, activation of caspase 3 protease via a Bcl-2-insensitive pathway, potentiate free-radical formation and accumulation of sphinganine. Programmed cell death is a highly conserved mechanism of self-defense, also found to occur in plants. Hence, it is natural to assume that chemicals must exist in them to regulate programmed cell death in them. Thus, plants are likely to prove to be important sources of agents that will modulate programmed cell death.

Chemical speciation influences comparative activity of selenium-enriched garlic and yeast in mammary cancer prevention.
J Agric Food Chem 2000 Sep;48(9):4452.
Ip C, Birringer M, Block E, Kotrebai M, Tyson JF, Uden PC, Lisk DJ.
Department of Experimental Pathology, Roswell Park Cancer Institute, Buffalo, NY 14263, USA. Clement.Ip@roswellpark.org

A recent human intervention trial showed that daily supplementation with selenized yeast (Se-yeast) led to a decrease in the overall cancer morbidity and mortality by nearly 50%; past research has also demonstrated that selenized garlic (Se-garlic) is very effective in mammary cancer chemoprevention in the rat model. The goal of this study was to compare certain biological activities of Se-garlic and Se-yeast and to elucidate the differences based on the chemical forms of selenium found in these two natural products. Characterization of organic selenium compounds in yeast (1922 microg/g Se) and garlic (296 microg/g Se) was carried out by high-performance liquid chromatography with inductively coupled plasma mass spectrometry or with electrospray mass spectrometry. Analytical speciation studies showed that the bulk of the selenium in Se-garlic and Se-yeast is in the form of gamma-glutamyl-Se-methylselenocysteine (73%) and selenomethionine (85%), respectively. The above methodology has the sensitivity and capability to account for >90% of total selenium. In the rat feeding studies, supplementation of Se-garlic in the diet at different levels consistently caused a lower total tissue selenium accumulation when compared to Se-yeast. On the other hand, Se-garlic was significantly more effective in suppressing the development of premalignant lesions and the formation of adenocarcinomas in the mammary gland of carcinogen-treated rats. Given the present finding on the identity of selenomethionine and gamma-glutamyl-Se-methylselenocysteine as the major form of selenium in Se-yeast and Se-garlic, respectively, the metabolism of these two compounds is discussed in an attempt to elucidate how their disposition in tissues might account for the differences in cancer chemopreventive activity.

Effects of garlic components diallyl sulfide and diallyl disulfide on arylamine N-acetyltransferase activity and 2-aminofluorene-DNA adducts in human promyelocytic leukemia cells.
Am J Chin Med. 2002;30(2-3):315-25.
Lin JG, Chen GW, Su CC, Hung CF, Yang CC, Lee JH, Chung JG.
Institute of Chinese Medical Science, China Medical College, Taichung, Taiwan, ROC.

Two components of garlic, diallyl sulfide (DAS) and diallyl disulfide (DADS), inhibited arylamine N-acetyltransferase (NAT) activity and 2-aminofluorene-DNA adduct in human promyelocytic leukemia cells (HL-60). The NAT activity was measured by high performance liquid chromatography assaying for amounts of N-acetyl-2-aminofluorene (2-AAF) and remaining 2-aminofluorene (2-AF). Cellular cytosols and intact cell suspensions were assayed. The inhibition of NAT activity and 2-AF-DNA adduct formation in human leukemia cells by DAS and DADS were dose-dependent and were directly proportional. The data also indicated that DAS and DADS decrease the apparent values of Km and Vmax from human leukemia cells in both assays. This is the first report of garlic components affecting human leukemia cell NAT activity and 2-AF-DNA adduct formation.

The electron probe microanalysis on oral precancer treated by garlic
Hunan Yi Ke Da Xue Xue Bao. 2000 Jun 28;25(3):231-2.
[Article in Chinese]
Tang ZG, Xu XP, Shen ZH.
Department of Oral and Maxillofacial Surgery, Xiangya Hospital.

OBJECTIVE: To evaluate the effect of 4 kinds of trace elements on experimental oral precancer treated by garlic. METHODS: The palatal mucosae of 42 Wistar rats were painted with 0.5% of 4-nitroquinololine-1-oxide(4NQO) three times weekly for 7 weeks by coating method. Then the animals were divided randomly into two groups. The treatment group was treated three times weekly with garlic solution at the posterior hard palatal mucosae by coating method, and in the control group, the vehicle-distilled water was used instead of garlic solution. At the 5th and 8th weeks of the treatment and the 7th week after the treatment was stopped, some animals were killed. The palatal epithelial cells were prepared and surveyed by electron probe microanalysis. RESULTS: During the treating period, garlic improved the levels of epithelial cells' nuclei copper, selenium, molybdenum and extranuclei selenium, molybdenum(P < 0.01), but it decreased the contents of epithelial cells' extranuclei copper and extra- and intranuclei zinc(P < 0.01). CONCLUSIONS: Garlic can treat the oral precancer by improving the levels of epithelial cells' nuclei copper, selenium, and molybdenum and extranuclei selenium and molybdenum.

Altered cytokeratin expression during chemoprevention of experimental hamster buccal pouch carcinogenesis by garlic.
J Oral Pathol Med. 2002 Mar;31(3):142-6.
Balasenthil S, Rao KS, Nagini S.
Department of Biochemistry, Faculty of Science, Annamalai University, Annamalainagar-608,002, Tamil Nadu, India.

BACKGROUND: Cytokeratins (also known as keratins (K)) are members of the family of intermediate filaments and form major components of the mammalian epithelial cell cytoskeleton. Cytokeratins have emerged as reliable cellular markers of oral cancer development and chemoprevention because of their abundance, stability and high antigenicity. METHODS: We investigated the effect of aqueous garlic extract on cytokeratin expression during 7,12-dimethylbenz[a]anthracene (DMBA)-induced hamster buccal pouch (HBP) carcinogenesis. Hamsters were divided into four groups of six animals. Animals in group 1 were painted with a 0.5% solution of DMBA in liquid paraffin, on the right buccal pouches, three times a week for 14 weeks. Group 2 animals were painted with DMBA as in group 1 and also received 250 mg/kg body weight aqueous garlic extract orally on alternate days to the DMBA application. Group 3 animals received garlic extract only, as in group 2. Group 4 animals received neither DMBA nor garlic extract and served as the control. The hamsters were killed after an experimental period of 14 weeks. RESULTS: Cytokeratin expression was studied using human monoclonal antibodies AE1 and AE3, which react with type I and II keratins. In DMBA-induced squamous cell carcinomas, decreased expression of high molecular weight keratins was observed. Administration of garlic extract to animals painted with DMBA suppressed HBP carcinomas and restored normal cytokeratin expression. CONCLUSION: The results of the present study suggest that inhibition of HBP carcinogenesis by garlic may be due to its regulatory effects on differentiation, tumour invasiveness, migratory and metastatic potential. We suggest that one of the mechanisms of tumour inhibition by garlic is an influence on cellular differentiation.

Garlic induces apoptosis during 7,12-dimethylbenz[a]anthracene-induced hamster buccal pouch carcinogenesis.
Oral Oncol. 2002 Jul;38(5):431-6.
Balasenthil S, Rao KS, Nagini S.
Department of Biochemistry, Faculty of Science, Annamalai University, Tamil Nadu, India.

The apoptosis-inducing capacity of aqueous garlic extract during 7,12-dimethylbenz[a]anthracene-induced hamster buccal pouch (HBP) carcinogenesis was investigated in male Syrian hamsters using DNA fragmentation and the apoptosis-associated proteins, tissue transglutaminase (tTG) and Bcl-2. Hamsters were divided into four groups of six animals each. Animals in group 1 were painted with a 0.5% solution of DMBA in liquid paraffin on the right buccal pouches three times a week for 14 weeks. Group 2 animals painted with DMBA as in group 1, in addition received 250 mg/kg body weight aqueous garlic extract orally on days alternate to DMBA application. Group 3 animals received garlic extract as in group 2. Group 4 animals received neither DMBA nor garlic extract and served as the control. The experiment was terminated at the end of 14 weeks. Administration of aqueous garlic extract (250 mg/kg body weight) to animals painted with DMBA inhibited DMBA-induced oral carcinogenesis as revealed by the absence of neoplasms, induction of tTG and inhibition of Bcl-2 expression. The results of the present study suggest that garlic may exert its chemopreventive effect by inducing apoptosis.

Garlic and cancer: a critical review of the epidemiologic literature.
Fleischauer AT, Arab L.
Department of Epidemiology, University of North Carolina at Chapel Hill, NC 27599, USA.

Animal and in vitro studies provide evidence of an anticarcinogenic effect of active ingredients in garlic. This review of the epidemiologic literature on garlic consumption addresses cancers of the stomach, colon, head and neck, lung, breast and prostate. Nineteen studies reported relative risk estimates for garlic consumption and cancer incidence. Site-specific case-control studies of stomach and colorectal cancer, in which multiple reports were available, suggest a protective effect of high intake of raw and/or cooked garlic. Cohort studies confirm this inverse association for colorectal cancer. Few cohort and case-control studies for other sites of cancer exist. Garlic supplements, as analyzed in four cohort studies and one case-control report, from two distinct populations, do not appear to be related to risk. Low study power, lack of variability in garlic consumption categorization within studies and poor adjustment for potential cofounders may limit the reliability of any conclusions regarding garlic supplements. However, an indication of publication bias was also found by visual inspection of a funnel plot and in a log-rank test (P = 0.004). Evidence from available studies nevertheless suggests a preventive effect of garlic consumption in stomach and colorectal cancers. The study limitations indicate the need for more definitive research and improved nutritional epidemiologic analyses of dietary data.

An intervention trial to inhibit the progression of precancerous gastric lesions: compliance, serum micronutrients and S-allyl cysteine levels, and toxicity.
Eur J Cancer Prev. 2001 Jun;10(3):257-63.
You WC, Chang YS, Heinrich J, Ma JL, Liu WD, Zhang L, Brown LM, Yang CS, Gail MH, Fraumeni JF Jr, Xu GW.
National Cancer Institute, Division of Cancer Epidemiology and Genetics, Bethesda, MD 20892, USA. youw@exchange.nih.gov

Gastric cancer is the second most frequent cause of death from cancer in the world and the leading cause of death from cancer in China. In September 1995, we launched a randomized multi-intervention trial to inhibit the progression of precancerous gastric lesions in Linqu County, Shandong Province, an area of China with one of the world's highest rates of gastric cancer. Treatment compliance was measured by pill counts and quarterly serum concentrations of vitamin C, vitamin E and S-allyl cysteine. In 1999, toxicity information was collected from each trial participant to evaluate treatment-related side-effects during the trial. Compliance rates were 93% and 92.9% for 39 months of treatment with the vitamins/mineral and garlic preparation, respectively. The means for serum concentrations of vitamins C and E were 7.2 microg/ml and 1695 microg/dl among subjects in the active treatment groups compared with 3.1 microg/ml and 752 microg/dl among subjects in the placebo treatment group, respectively. No significant differences in side-effects were observed between the placebo treatment group and the vitamins/mineral and garlic preparation treatment groups during the 39-month trial period.

Mechanisms by which garlic and allyl sulfur compounds suppress carcinogen bioactivation. Garlic and carcinogenesis.
Adv Exp Med Biol. 2001;492:69-81.Milner JA.
Nutrition Department, The Pennsylvania State University, University Park, 16802, USA.

Overall, a host of studies provides compelling evidence that garlic and its organic allyl sulfur components are effective inhibitors of the cancer process. These studies reveal that the benefits of garlic are not limited to a specific species, to a particular tissue, or to a specific carcinogen. Several mechanisms are likely to account for this protection. Notable among these is a depression in nitrosamine formation and a reduction in carcinogen bioactivation. The benefits provided by garlic must be viewed as part of the entire diet, since several dietary constituents can influence the degree of protection. More than one compound is responsible for the anticancer properties associated with garlic. Future research should focus on how genetic variability and daily environmental factors influence the anticancer benefits attributed to garlic and its allyl sulfur components.

Enhanced immunocompetence by garlic: role in bladder cancer and other malignancies.
J Nutr. 2001 Mar;131(3s):1067S-70S.Lamm DL, Riggs DR.
Department of Urology, Robert C. Byrd Health Science Center West Virginia University, Morgantown, WV 26506-9251, USA. Dlamm@wvuhsc1.hsc.wvu.edu

Of the many beneficial actions of garlic, inhibition of the growth of cancer is perhaps the most remarkable. Our previous animal studies demonstrated that aged garlic extract was highly effective, and unlike the approved immunotherapy for human bladder cancer, bacillus Calmette--Guerin (BCG), garlic was effective when added to the diet. To elucidate the mechanism of this antitumor effect, the literature describing antitumor and immune-enhancing effects of garlic is reviewed. Garlic can detoxify carcinogens by stimulation of cytochrome P(450) enzymes, antioxidant activity or sulfur compound binding. Studies demonstrate a direct toxic effect of garlic to sarcoma and gastric, colon, bladder and prostate cancer cells in tissue culture, but these effects cannot explain the inhibition of growth of transplanted cancer in animal models. The most likely explanation of this effect is immune stimulation. Comparison of the effects of garlic to BCG immunotherapy reveals many similarities. Both stimulate proliferation of lymphocytes and macrophage phagocytosis, induce the infiltration of macrophages and lymphocytes in transplanted tumors, induce splenic hypertrophy, stimulate release of interleukin-2, tumor necrosis factor-alpha and interferon-gamma, enhance natural killer cell, killer cell and lymphokine-activated killer cell activity. These activities represent effective stimulation of the immune response. Studies suggest that garlic may be useful in preventing the suppression of immune response that is associated with increased risk of malignancy. Data suggest that maintenance of immune stimulation can significantly reduce the risk of cancer. Clinical trials should be initiated to test the hypothesis that the immune stimulation and other beneficial effects of garlic are able to reduce the incidence of cancer.

Allium sativum potentiates suicide gene therapy for murine transitional cell carcinoma.
Nutr Cancer. 2000;38(1):98-105
Moon DG, Cheon J, Yoon DH, Park HS, Kim HK, Kim JJ, Koh SK.
Department of Urology, Korea University College of Medicine, Seoul, Korea.

This study evaluated the synergistic effect of Allium sativum (AS) with suicide gene therapy for transitional cell carcinoma (TCC) of the bladder. Subcutaneous TCCs were established in syngeneic C3H/He mice with 1 x 10(5) MBT-2 cells. AS liquid extract was injected at the site of tumor transplantation on Day 1 for three weeks (Experiment I) and into the established tumors weekly for five weeks (Experiment II) in combination with or without gene therapy using a replication-defective adenoviral vector containing a herpes simplex virus thymidine kinase (HSV-TK) gene under the transcriptional control of Rous sarcoma virus (RSV) promoter (Ad-RSV-TK, 5 x 10(8) plaque-forming units) plus ganciclovir (20 mg/kg/day i.p.). AS demonstrated a statistically significant reduction in incidence of TCC (cumulative dose 25 mg of AS). Combination AS-suicide gene therapy significantly inhibited the tumor growth compared with the controls, which was evidenced by apoptosis on histomorphological and immunohistochemical studies. These results suggest that AS had a definite antitumor effect in inhibiting tumorigenesis and growth of TCC in a murine model. AS treatment combined with suicide gene therapy had significant additive antitumor effects on TCC and may provide a novel and effective treatment modality for TCC of the bladder.

Allium sativum (garlic) treatment for murine transitional cell carcinoma.
Cancer. 1997 May 15;79(10):1987-94.
Riggs DR, DeHaven JI, Lamm DL.
Department of Urology, West Virginia University School of Medicine, Morgantown 26506, USA.

BACKGROUND: Currently, immunotherapy with Bacillus Calmette-Guerin (BCG) is the most effective treatment for superficial bladder carcinoma, but treatment-related toxicity may limit its use in some patients. Alternative treatments are needed for patients who fail to respond to BCG immunotherapy. Allium sativum (AS), or garlic, is known to have a broad range of biologic activities, including immune stimulation and reported antitumor activity. For these reasons, the authors conducted a series of experiments designed to explore the possible therapeutic effects of AS in the MBT2 murine bladder carcinoma model. METHODS: C3H/HeN mice were randomized prior to initiation of each experimental protocol. Mice received 1 x 10(3) MBT2 cells in 0.1 mL RPMI-1640, administered subcutaneously into the right thigh, on Day 0 of the experiment. AS was injected at the site of tumor transplantation on Day 1 and at 2- to 7-day intervals up to Day 28. To evaluate the effects of oral AS in this model, treatment was initiated 30 days prior to tumor inoculation and continued for 30 days after tumor inoculation. Animals in all experiments were followed for tumor incidence, tumor growth, and survival. RESULTS: In the initial experiments, subcutaneous AS significantly reduced tumor volume compared with the saline control (P < 0.05). Unfortunately, treatment-related death was also observed, requiring reduction in the total dose of AS. Animals that received 5 weekly immunizations of AS (5 mg, 5 mg, 1 mg, 1 mg, and 1 mg; cumulative dose = 13 mg) had significantly reduced tumor incidence, tumor growth, and increased survival when compared with animals that received the saline control. No treatment-related deaths were observed with this treatment schedule. To determine whether systemic AS administration might be effective, orally administered AS was tested at doses of 5 mg, 50 mg, and 500 mg per 100 mL of drinking water. Mice that received 50 mg oral AS had significant reductions in tumor volume (P < 0.05) when compared with animals that received the saline control, and mice that received 500 mg oral AS had significant reductions in both tumor volume and mortality (P < 0.05). CONCLUSIONS: The significant antitumor efficacy of subcutaneous and oral AS warrants further investigation and suggests that AS may provide a new and effective form of therapy for transitional cell carcinoma of the bladder.

Flow cytometric analysis of the garlic oil effect on DNA content of cancer cell cycle
Zhongguo Zhong Xi Yi Jie He Za Zhi. 1992 Feb;12(2):92-4, 69-70.
[Article in Chinese]
Xie JY, Gao YM, Shen LC.
Institute of Basic Theory of TCM, China Academy of TCM, Beijing.

Flow cytometry (FCM) is a new technique developed in the recent decade. This technique may measure DNA content of 5000 cells per second and trace the dynamic changes in cell proliferation cycle and offer a hint for designing clinical treatment protocol, monitor prognosis and elucidate the mechanisms of antitumor drugs. The authors previous studies showed significant effect of garlic oil on prolongation of life expectancy and inhibition of tumor growth in mice. Using FCM the authors analysed the effect of garlic oil on cell cycle in S180 tumor cells, 2-6 hrs after single administration or multiple administration the cell number in S phase rapidly decreased, in G1 phase increased. This suggests garlic oil may blockade cells to progress from G1 phase to S phase and result in accumulation of cells in G1 phase and directly inhibit the synthesis of DNA and the cell cycle. Theoretical basis for clinical application was offered and some aspects of antitumor mechanism of garlic oil were elucidated.

Effect of garlic, Chinese medicinal drugs and amino acids on growth of Erlich ascites tumor cells in mice.
Am J Chin Med. 1983;11(1-4):69-73.
Choy YM, Kwok TT, Fung KP, Lee CY.

A number of food materials or drugs have been screened for the effect on the growth and development of transplantable Ehrlich ascites tumor cells. Growth of tumor-bearing mice was significantly inhibited by feeding garlic as well as some amino acids. These materials significantly reduced the total number of free tumor cells growing in the peritoneal cavity of mice and prolonged significantly the length of time for 50% death of tumor-bearing mice.

Factorial trial of three interventions to reduce the progression of precancerous gastric lesions in Shandong, China: design issues and initial data.
Control Clin Trials. 1998 Aug;19(4):352-69.
Gail MH, You WC, Chang YS, Zhang L, Blot WJ, Brown LM, Groves FD, Heinrich JP, Hu J, Jin ML, Li JY, Liu WD, Ma JL, Mark SD, Rabkin CS, Fraumeni JF Jr, Xu GW.
Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, Maryland 20892, USA.

Resumo : In the fall of 1995, 3411 subjects in 13 rural villages in Linqu County, Shandong Province, China, began participating in a blinded, randomized 23 factorial trial to determine whether interventions can reduce the prevalence of dysplasia and other precancerous gastric lesions. One intervention is treatment for infection by Helicobacter pylori with amoxicillin and omeprazole. A second is dietary supplementation with capsules containing vitamin C, vitamin E, and selenium. A third is dietary supplementation with capsules containing steam-distilled garlic oil and Kyolic aged garlic extract. Investigators will evaluate histopathologic endpoints after gastroscopies with biopsies from seven standard sites in 1999. Initial data from pill counts and sampled blood levels of vitamin E, vitamin C, and S-allylcysteine indicate excellent compliance. Subjects have tolerated all interventions well, although 3.1% of those assigned to amoxicillin and omeprazole developed rashes, compared to 0.3% to those in the control group. Preliminary breath tests demonstrate substantial reductions in gastric urease activity, an indication of infection by Helicobacter pylori, among those assigned to amoxicillin and omeprazole.

Helicobacter pylori infection, garlic intake and precancerous lesions in a Chinese population at low risk of gastric cancer.
Int J Epidemiol. 1998 Dec;27(6):941-4.
You WC, Zhang L, Gail MH, Ma JL, Chang YS, Blot WJ, Li JY, Zhao CL, Liu WD, Li HQ, Hu YR, Bravo JC, Correa P, Xu GW, Fraumeni JF Jr.
National Cancer Institute, Bethesda, MD 20892, USA.

BACKGROUND: Cangshan County of Shandong Province has one of the lowest rates of gastric cancer (GC) in China. While intestinal metaplasia (IM) and dysplasia (DYS) are less common in Cangshan than in areas of Shandong at high risk of GC, these precursor lesions nevertheless affect about 20% of adults age > or = 55. SUBJECTS AND SETTING: In order to evaluate determinants of IM and DYS in Cangshan County, a low risk area of GC a survey was conducted among 214 adults who participated in a gastroscopic screening survey in Cangshan County in 1994. METHOD: A dietary interview and measurement of serum Helicobacter pylori antibodies were performed. RESULTS: The prevalence of H. pylori was lowest (19%) among those with normal gastric mucosa, rising steadily to 35% for superficial gastritis (SG), 56% for chronic atrophic gastritis (CAG), 80% for IM, and 100% for DYS. The prevalence odds of precancerous lesions were compared with the odds of normal histology or SG. The odds ratio (OR) or CAG associated with H. pylori positivity was 4.2 (95% confidence interval [CI] : 1.7-10.0), while the OR of IM/DYS associated with H. pylori positivity was 31.5 (95% CI: 5.2-187). After adjusting for H. pylori infection, drinking alcohol was a risk factor for CAG (OR = 3.2, 95% CI: 1.1-9.2) and IM/DYS (OR = 7.8, 95% CI: 1.3-47.7). On the other hand, consumption of garlic showed non-significant protective effects and an inverse association with H. pylori infection. CONCLUSIONS: The findings of this study suggest that infection with H. pylori is a risk factor and garlic may be protective, in the development and progression of advanced precancerous gastric lesions in an area of China at relatively low risk of GC.

Inhibition of N-acetyltransferase activity and gene expression in human colon cancer cell lines by diallyl sulfide.
Food Chem Toxicol. 2004 Feb;42(2):195-202.
Chung JG, Lu HF, Yeh CC, Cheng KC, Lin SS, Lee JH.
Department of Microbiology, China Medical University, No 91 Hsueh-Shih road, 400 Taichung, Taiwan, Republic of China.

Diallyl sulfide (DAS) is one of the major components of garlic (Allium sativum) and is widely used in the world for food. In this study, DAS was selected for testing the inhibition of arylamine N-acetyltransferase (NAT) activity (N-acetylation of 2-aminofluorene) and gene expression (mRNA NAT) in human colon cancer cell lines (colo 205, colo 320 DM and colo 320 HSR). The NAT activity was examined by high performance liquid chromatography and indicated that a 24 h DAS treatment decreases N-acetylation of 2-aminofluorene in three colon (colo 205, 320 DM and colo 320 HSR) cancer cell lines. The NAT enzymes (protein) were analyzed by western blotting and flow cytometry and it indicated that DAS decreased the levels of NAT in three colon (colo 205, 320 DM and colo 320 HSR) cancer cell lines. The gene expression of NAT (mRNAT NAT) was determined by polymerase chain reaction (PCR), it was shown that DAS affect mRNA NAT expression in examined human colon cancer cell lines. This report is the first to demonstrate that DAS does inhibit human colon cancer cell NAT activity and gene expression.

Retinoic acid receptor-beta mRNA expression during chemoprevention of hamster cheek pouch carcinogenesis by garlic.
Asia Pac J Clin Nutr. 2003;12(2):215-8.
Balasenthil S, Rao KS, Nagini S.
Department of Biochemistry, Faculty of Science, Annamalai University, Annamalainagar, Tamil Nadu, India.

The effect of aqueous garlic (Allium sativum Linn.) on retinoic acid receptor beta (RARbeta) mRNA expression was investigated in male Syrian hamsters during 12-dimethyl enz[a]anthracene (DMBA)-induced hamster buccal pouch (HBP) carcinogenesis. RARbeta mRNA expression was analysed by slot blotted hybridization with radiolabelled RAR-beta probe. In DMBA-induced HBP tumours, decreased expression of RARbeta mRNA was observed. Administration of garlic (250mg/kg body weight) to animals painted with DMBA restored RARbeta mRNA expression to normal pattern suggesting that this may be one of the mechanisms by which garlic exerts its chemopreventive effects.

Tomato and garlic can modulate azoxymethane-induced colon carcinogenesis in rats.
Eur J Cancer Prev. 2003 Jun;12(3):195-200.Sengupta A, Ghosh S, Das S.
Department of Cancer Chemoprevention, Chittaranjan National Cancer Institute 37, Kolkata, India. archanadi1@rediffmail.com

Tomato (Lycopersicon esculentum) and garlic (Allium cepa) are important constituents of the human diet. Compounds like diallyl sulfides, diallyl disulfides and quercetin, which are active components of garlic, have known anti-inflammatory, antimutagenic activities. Similarly, active components in tomato, such as kaempferol and chlorogenic acid, have antimutagenic activities and lycopene is the most active oxygen quencher with potential chemopreventive activities. In view of this, an endeavour was made to evaluate the anticarcinogenic effect, if any, of tomato and garlic consumption individually and in combination on azoxymethane-induced colonic precancerous lesion, the aberrant crypt foci in animal model. Sprague-Dawley rats (4-5 weeks old) were injected with azoxymethane (15 mg/kg b.w.) and orally administered with 2% (w/v) of tomato, garlic and a combination of both. After 12 weeks of first azoxymethane injection, colons were assessed for aberrant crypt foci and compared with the carcinogen control group. Lipid peroxidation level and glutathione-S-transferase (GST) activity were assessed in liver as well as in colon. Furthermore, in situ cell proliferation and apoptosis were estimated using the Brdu incorporation method and TUNEL method respectively. It was observed that aberrant crypt foci were reduced in all treated groups (by 32.11% in garlic, by 76.14% in tomato and by 55.96% in the combination group). Among treated groups, GST activity was found to be induced in both liver and colon, whereas considerable reduction in lipid peroxidation level was observed in liver as well as in colon with respect to the carcinogen control group. Significant reduction in Brdu labelling index and increase in apoptotic index in colon was noted in the treated groups. These results suggest that tomato and garlic suspensions have a protective effect on colon carcinogenesis, which is mediated by modulation of different biological pathways during carcinogenesis.

Garlic [Allium sativum]: a review of its potential use as an anti-cancer agent.
Curr Cancer Drug Targets. 2003 Feb;3(1):67-81.
Thomson M, Ali M.
Deptartment of Biological Sciences, Faculty of Science, Kuwait University, P O Box 5969, 13060 - Safat, Kuwait. martha@kuc01.kuniv.edu.kw

Garlic [Allium sativum] is among the oldest of all cultivated plants. It has been used as a medicinal agent for thousands of years. It is a remarkable plant, which has multiple beneficial effects such as antimicrobial, antithrombotic, hypolipidemic, antiarthritic, hypoglycemic and antitumor activity. In this review, we will discuss particularly the largely preclinical use of this agent in the treatment and prevention of cancer. A number of studies have demonstrated the chemopreventive activity of garlic by using different garlic preparations including fresh garlic extract, aged garlic, garlic oil and a number of organosulfur compounds derived from garlic. The chemopreventive activity has been attributed to the presence of organosulfur compounds in garlic. How this is achieved is not fully understood, but several modes of action have been proposed. These include its effect on drug metabolizing enzymes, antioxidant properties and tumor growth inhibition. Most of these studies were carried out in the animal models. Also, recent research has focused on the antimutagenic activity of garlic. Recently, it has been observed that aged garlic extract, but not the fresh garlic extract, exhibited radical scavenging activity. The two major compounds in aged garlic, S-allylcysteine and S-allylmercapto-L-cysteine, had the highest radical scavenging activity. In addition, some organosulfur compounds derived from garlic, including S-allylcysteine, have been found to retard the growth of chemically induced and transplantable tumors in several animal models. Therefore, the consumption of garlic may provide some kind of protection from cancer development.

Study of anti-tumor action and influence on immune function of Allium stativum
Zhong Yao Cai. 1998 May;21(5):240-3.
[Article in Chinese]
Li Q, Li S, Yang G.
Jinan University, Guangzhou 510632.

Applying mice test on cancer model of S180 and Lewis cancer by using method clystered stomach(oral), observs the Anti-tumor function. Experiments showed that Allium sativum can inhibit tumor growth and Lengthen lift duration of mice, the rate of inhibiting tumor was 74.35% and life lengthening rate were 42.4%, with control grou comparison. There was profund difference between them. Besides, we discoved Allium sativum can raise immune function of mice.

Allium v egetables and risk of prostate cancer: a population-based study.
J Natl Cancer Inst. 2002 Nov 6;94(21):1648-51
Hsing AW, Chokkalingam AP, Gao YT, Madigan MP, Deng J, Gridley G, Fraumeni JF Jr.
Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD 20892-7234, USA. hsinga@mail.nih.gov

Epidemiologic and laboratory studies suggest that allium vegetables and garlic constituents have antitumor effects. In a population-based, case-control study conducted in Shanghai, China, we investigated the association between intake of allium vegetables, including garlic, scallions, onions, chives, and leeks, and the risk of prostate cancer. We administered in-person interviews and collected information on 122 food items from 238 case subjects with incident, histologically confirmed prostate cancer and from 471 male population control subjects. Men in the highest of three intake categories of total allium vegetables (>10.0 g/day) had a statistically significantly lower risk (odds ratio [OR] = 0.51, 95% confidence interval [CI] = 0.34 to 0.76; P(trend)<.001) of prostate cancer than those in the lowest category (<2.2 g/day). Similar comparisons between categories showed reductions in risk for men in the highest intake categories for garlic (OR = 0.47, 95% CI = 0.31 to 0.71; P(trend)<.001) and scallions (OR = 0.30, 95% CI = 0.18 to 0.51; P(trend)<.001). The reduced risk of prostate cancer associated with allium vegetables was independent of body size, intake of other foods, and total calorie intake and was more pronounced for men with localized than with advanced prostate cancer.

Critical role of allyl groups and disulfide chain in induction of Pi class glutathione transferase in mouse tissues in vivo by diallyl disulfide, a naturally occurring chemopreventive agent in garlic.
Carcinogenesis. 2002 Oct;23(10):1661-5.
Bose C, Guo J, Zimniak L, Srivastava SK, Singh SP, Zimniak P, Singh SV.
Department of Medicine, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA.

We have shown previously that the chemoprotective activity of diallyl disulfide (DADS), a naturally occurring anticancer agent in garlic, against benzo[a]pyrene (BP)-induced forestomach carcinogenesis in mice correlates strongly with its inductive effects on the expression of Pi class glutathione (GSH) transferase mGSTP1-1. The present structure-activity relationship studies were designed to define the role of allyl groups and the disulfide chain in mGSTP1-inducing activity of DADS. Hepatic mGSTP1 mRNA levels rose rapidly upon treatment of mice with DADS, reached a maximum between 12 and 24 h (< or =5.7-fold induction) and fell to control levels by 48 h after DADS treatment. Induction of mGSTP1 mRNA in the forestomach was maximal between 6 and 12 h after DADS treatment (< or =4.7-fold induction). The mGSTP1 mRNA expression was either unaltered (liver) or moderately increased (forestomach) upon treatment of mice with dipropyl disulfide (DPDS), which is a naturally occurring saturated analog of DADS. These results indicated that the allyl groups are critical for the mGSTP1-inducing activity of DADS. A statistically significant increase in the expression of mGSTP1 mRNA was also observed in the liver and forestomach of mice treated with diallyl monosulfide (DAMS), albeit to a much lesser extent compared with DADS. These results indicated that the oligosulfide chain length in garlic organosulfides (OSCs) is equally important for their mGSTP1-inducing activity. The role of the disulfide chain in DADS-mediated induction of mGSTP1 was further investigated by testing a pair of alkadienes (1,7-octadiene and 1,8-nonadiene) having structural similarity to DADS. Both DADS and the alkadienes carry allyl groups at both ends of a linear molecule and the distance between the allylic carbon atoms is similar in both compounds, but the central disulfide chain of DADS is replaced with an alkyl chain in the alkadienes. The alkadienes were either ineffective or moderately active in increasing mGSTP1 expression. In conclusion, the results of the present study clearly indicate that the presence of terminal allyl groups as well as the central disulfide chain is required for maximum induction of mGSTP1 in vivo by garlic-derived OSCs.

Study on trace elements in epithelial cells during oral carcinogenesis prevented by garlic
Hunan Yi Ke Da Xue Xue Bao. 2000 Feb 28;25(1):27-9.

Tang ZG, Xu XP, Shen ZH.
Department of Oral and Maxillofacial Surgery, Xiangya Hospital.

Sixty-two Wistar rats were divided randomly into two groups, thirty-one for each group. The posterior hard palatal mucosae of all animals were painted thrice weekly with 0.5% 4-nitroquinoline 1-oxide(dissolved in dimethyl sulfoxide). Before that, the garlic injection solution and the distilled water were painted at the same place of the experimental and control group animals, respectively. All animals were killed in turn from the beginning of the experiment at random at the 10th, 13th, and 19th week. Then, trace elements of intranuclear and cytoplasm of epithelial cells or cancer cells at the mentioned weeks were surveyed by electron probe microanalysis. The results were that garlic decreased the levels of intranuclear and cytoplasm copper(P < 0.05); the levels of intranuclear and cytoplasm selenium at the 10th week and the 13th week(P < 0.05) and those of zinc at the 19th week (P < 0.01) increased. So, garlic inhibits oral carcinogenesis by changing concentrations of intranuclear and cytoplasm trace elements that is copper, zinc, selenium, and the ratio of the three elements.

Emblica officinalis

Identification of pyrogallol as an antiproliferative compound present in extracts from the medicinal plant Emblica officinalis: effects on in vitro cell growth of human tumor cell lines.

Int J Oncol;21(1):187-92, 2002 Jul. Khan MT; Lampronti I; Martello D; Bianchi N; Jabbar S; Choudhuri MS; Datta BK; Gambari R

Pharmacology Research Laboratory, Faculty of Pharmaceutical Sciences, University Science and Technology Chittagong, Bangladesh.