Mechanisms of prostate carcinogenesis and its prevention by a γ-tocopherol-rich mixture of tocopherols in TRAMP mice

Tocopherols belong to a subgroup of the vitamin E family. Dietary feeding of a γ-tocopherol-rich mixture of tocopherols (γ-TmT) inhibits prostate tumorigenesis in TRAMP mice. In this study, we aimed to investigate mechanisms of prostate carcinogenesis in TRAMP mice by identifying differentially expressed pathways and effects of γ-TmT on these pathways. Eight-week-old TRAMP and age-matched C57BL/6 mice were administered either 600 mg/kg of γ-TmT or a control vehicle via oral gavage. Twelve hours after dosing, prostate tissues were collected for RNA extraction. Whole genome mouse microarrays were used to examine gene expression profiles. The expression of the selected genes were validated using quantitative PCR. Thousands of genes and various pathways were altered in the prostates of TRAMP mice. Compared to C57BL/6 mice, TRAMP mice exhibited enhanced proliferation, suppressed expression of antioxidant and phase II detoxification enzymes, and metabolic reprogramming in the prostate. γ-TmT differentially regulated the gene expression profiles of TRAMP and C57BL/6 mice, with only a small percentage of genes overlapping. γ-TmT inhibited genes involved in proliferation and glucose metabolism and induced several antioxidant/phase II detoxification genes in TRAMP mice. γ-TmT modulates multiple aberrant pathways in the prostate of TRAMP mice, which might represent important mechanisms for prostate cancer prevention.