The biological activities of
tocotrienols are receiving increasing attention. Herein, we report the efficacy of a mixed-
tocotrienol diet against prostate
tumorigenesis in the transgenic
adenocarcinoma mouse prostate (TRAMP) mouse model. Male TRAMP mice, 8 wk old, were fed 0.1%, 0.3%, or 1% mixed
tocotrienols in AIN-76A diet up to 24 wk old. Likewise, a positive control group consisting of male TRAMP mice and a negative control group consisting of wild-type nontransgenic mice were fed regular AIN-76A diet up to 24 wk old. Our results show that mixed-
tocotrienol-fed groups had a lower incidence of
tumor formation along with a significant reduction in the average wet weight of genitourinary apparatus. Furthermore, mixed
tocotrienols significantly reduced the levels of high-grade neoplastic lesions as compared to the positive controls. This decrease in levels of high-grade neoplastic lesions was found to be associated with increased expression of proapoptotic
proteins BAD (Bcl(2) antagonist of cell death) and cleaved
caspase-3 and
cell cycle regulatory proteins cyclin dependent kinase inhibitors p21 and p27. In contrast, the expression of
cyclins A and E were found to be decreased in mixed-
tocotrienol groups. Taken together, our results show that by modulating
cell cycle regulatory proteins and increasing expression of proapoptotic
proteins, mixed
tocotrienols suppress prostate
tumorigenesis in the TRAMP mice.