Equol and genistein enhance the apoptotic effects of γ-tocotrienol in prostate cancer LNCaP cells. Free

B80

Prostate cancer is one of the most common male cancers in Western countries, yet the incidence of this fatal disease remains low in Asian populations. Environmental factors such as diet play an important role in cancer etiology, and a high phytoestrogen intake may be one factor contributing to the low prostate cancer mortality in Eastern populations. In this study, we investigated the possible combined effect of γ-tocotrienol, a vitamin E acylic isoprenoid (found in rice) with the phytoestrogens genistein, daidzein (found in soybeans) and equol (a daidzein metabolite) on cell growth and apoptosis in three human prostate tumor cell lines. The cell lines included in this study are the androgen receptor-positive LNCaP, and the androgen receptor-negative PC3 and DU-145. Similarly to what we found in an earlier study (Free Radical Research, 36: 116-118, 2002) γ-tocotrienol inhibited the growth of all three-cell lines in a dose-dependent manner. However, morphologic features of apoptosis and caspase-3 activation were limited to LNCaP cells. Cleaved poly (ADP-ribose) polymerase (PARP) was elevated in a dose-dependent manner with γ-tocotrienol concentrations ranging from 10-100 μM. Both genistein and equol, at a concentration of 10 μM, enhanced the effect of γ-tocotrienol on caspase-3 activation whereas daidzein had no effect. These results show clearly that the growth inhibitory and apoptotic effects of γ-tocotrienol are augmented in the presence of genistein or equol. However, these effects are limited to androgen-responsive cells. This is the first report, to our knowledge, providing evidence that components of soy enhance the anticancer effect of the rice component γ-tocotrienol.