Mechanisms of prostate carcinogenesis and its prevention by a γ-tocopherolrich mixture of tocopherol

来源 :Journal of Chinese Pharmaceutical Sciences | 被引量 : 0次 | 上传用户:xielongj_30
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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 carcinogenesisin TRAMP mice by identifying differentially expressed pathways and effects of γ-TmT on these pathways. Eight-week-oldTRAMP 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 toexamine gene expression profiles. The expression of the selected genes were validated using quantitative PCR. Thousands ofgenes and various pathways were altered in the prostates of TRAMP mice. Compared to C57BL/6 mice, TRAMP mice exhibitedenhanced proliferation, suppressed expression of antioxidant and phase II detoxification enzymes, and metabolic reprogrammingin the prostate. γ-TmT differentially regulated the gene expression profiles of TRAMP and C57BL/6 mice, with only a smallpercentage of genes overlapping. γ-TmT inhibited genes involved in proliferation and glucose metabolism and induced severalantioxidant/phase II detoxification genes in TRAMP mice. γ-TmT modulates multiple aberrant pathways in the prostate ofTRAMP mice, which might represent important mechanisms for prostate cancer prevention. 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 Eight-week-old TRAMP and age-matched C57BL / 6 mice were either administered 600 mg / kg of γ-TmT or a control vehicle via oral gavage. Weld hours after dosing The genome 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 exhibitedenhanced proliferation, suppressed expression of antioxidant and phase II detoxification enzymes, and metabolic reprogramming in the prostate. Γ-TmT di γ-TmT inhibited genes involved in proliferation and glucose metabolism and induced severalantioxidant / 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.
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