Gamma tocotrienol and prostate cancer: The regulation of two independent pathways to potentiate cell growth inhibition and apoptosis

Dietary vitamin E, highly expressed in palm oil, exists as either tocopherols or tocotrienols. Evidence indicates that vitamin Es may be potent cancer preventive agents. In this study, the gamma- and delta- isoforms of vitamin E were found to be the most effective at cancer cell growth inhibition, with the tocotrienols being more effective than the tocopherols in androgen-independent PC-3 prostate cancer cells. To assure that these compounds were selective toward cancer cells, the growth arrest of PrEC normal prostate cells was compared to PC-3 cells. At concentrations of -30 mu M dietary, gamma-vitamin Es showed no significant growth arrest on PrEC cell growth, but selectively inhibited growth in the PC-3 cancer cells. Moreover gamma-tocotrienol demonstrated a greater potential to inhibit growth in cancer cells at these lower concentrations than did gamma-tocopherol. Two independent pathways important in carcinogenesis were tested: PPAR gamma and NF kappa B. The PPAR gamma was up regulated by both dietary gamma-vitamin Es by the modulation of the endogenous ligand 15-S-HETE, while NE kappa B was only regulated by gamma-tocotrienol. The modulation of NF kappa B was confirmed by the down regulation of the pro-apoptotic proteins cIAP, xIAP, and BcL-2 which potentiate apoptosis and are down stream effectors of NF kappa B.