22/11/2009

                                                                                  José de Felippe Jr.

Lembremos que o ácido lipóico ativando a piruvato dehidrogenase é uma das substâncias que abrem as portas das mitocôndrias para o piruvato citoplasmático caminhar para a fosforilação oxidativa. O aumento da produção de ATP corre paralelo com o aumento da produção de radicais livres.
Se conseguimos aumentar a produção de ATP em célula transformada (célula cancerosa para muitos e célula em sofrimento necessitando de cuidados para nós), ela pára de se reproduzir e segue a via normal de morte celular que é a apoptose.

Increased ROS generation and p53 activation in alpha-lipoic acid-induced apoptosis of hepatoma cells
Apoptosis. 2007 Jan;12(1):113-23
Simbula G, Columbano A, Ledda-Columbano GM, Sanna L, Deidda M, Diana A, Pibiri M.
Department of Toxicology, Oncology and Molecular Pathology Unit, Italy.
Alpha-lipoic acid (alpha-LA) is an antioxidant used for the treatment of a variety of diseases, including liver cirrhosis, heavy metal poisoining, and diabetic polyneuropathy. In addition to its protective effect against oxidative stress, alpha-LA induces apoptosis in different cancer cells types. However, whether alpha-LA acid induces apoptosis of hepatoma cells is unknown. Herein, we investigated whether alpha-LA induces apoptosis in two different hepatoma cell lines FaO and HepG2. The results showed that alpha-LA inhibits the growth of both cell lines as indicated by the reduction in cell number, the reduced expression of cyclin A and the increased levels of the cyclin/CDKs inhibitors, p27(Kip1) and p21(Cip1). Cell cycle arrest was associated with cell loss, and DNA laddering indicative of apoptosis. Apoptosis was preceded by increased generation of reactive oxygen species, and associated with p53 activation, increased expression of Bax, release of cytochrome c from mitochondria, caspases activation, decreased levels of survivin, induction of pro-apoptotic signaling (i.e JNK) and inhibition of anti-apoptotic signaling (i.e. PKB/Akt) pathways. In conclusion, this study provides evidence that alpha-LA induces apoptosis in hepatoma cells, describes a possible sequence of molecular events underlying its lethal effect, and suggests that it may prove useful in liver cancer therapy.
PMID: 17136495