Journal of Oil Palm Research Vol. Special Issue  2008 Oct p.  33-43

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

Author(s): CAMPBELL, S.E. * ; WHALEY, S.G. * ; PHILLIPS, R. * ; AGGARWAL, B.B. + ; STIMMEL, J.B. ++ ; LEESNITZER, L. ++ ; BLANCHARD, S.G. ++ ; STONE, W.L. ** ; MUENYI, Christian ** ; KRISHNAN, K. *

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 γ- and δ- 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 μM dietary, γ-vitamin Es showed no significant growth arrest on PrEC cell growth, but selectively inhibited growth in the PC-3 cancer cells. Moreover γ-tocotrienol demonstrated a greater potential to inhibit growth in cancer cells at these lower concentrations than did γ-tocopherol. Two independent pathways important in carcinogenesis were tested: PPAR γ and NFκB. The PPAR γ was up regulated by both dietary γ-vitamin Es by the modulation of the endogenous ligand 15-S-HETE, while NFκB was only regulated by γ-tocotrienol. The modulation of NFκB 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 NFκB.

Keywords: , , , ,

Author Information
* Departments of Internal Medicine, East Tennessee State University, Johnson City, TN 37614, USA.

** Departments of Internal Medicine and Pediatrics East Tennessee State University, Johnson City, TN 37614, USA.

+ The U.T. M.D. Anderson Cancer Centre, Houston, TX 77030, USA.

++ Glaxo-Smith Kline Inc., Research Triangle Park, NC 27709, USA.

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