In vitro and in vivo modulation of testosterone mediated alterations in apoptosis related proteins by [6]-gingerol.

Ginger (Zingiber officinale, Zingiberaceae) has been widely used as a dietary spice, and as a traditional oriental medicine. The rhizome of ginger contains pungent vanillyl ketones, including [6]-gingerol and [6]-paradol, and have been credited with therapeutic and preventive health benefits, including anti-cancer activity. Prostate cancer is an attractive target for chemoprevention because of its ubiquity, treatment-related morbidity, long latency between premalignant lesions and clinically evident cancer, and defined molecular pathogenesis. Here we are reporting the modulatory effects of [6]-gingerol on testosterone-induced alterations on apoptosis related proteins in both in vitro, androgen sensitive LNCaP cells and in vivo, ventral prostate of Swiss albino mice. [6]-gingerol treatment resulted apoptosis in LNCaP cells, as indicated by depolarization of mitochondrial membrane potential, increase in sub G1 cell population by flow cytometry and the appearance of DNA laddering pattern in agarose gel electrophoresis. Results of western blot analysis showed that [6]-gingerol upregulated the testosterone depleted levels of p53 in mouse prostate and upregulated its downstream regulator Bax and further activated Caspase-9 and Caspase-3 in both LNCaP cells and in mouse prostate. We also found downregulation of testosterone induced antiapoptotic proteins, Bcl-2 and Survivin expression by [6]-gingerol in both LNCaP cells and in mouse ventral prostate. Thus, [6]-gingerol shows its protective effects in both in vivo and in vitro prostate cancer models by modulation of proteins involved in apoptosis pathway.