"It is unclear how accurately the biological activity of -tocopherol is modeled by the PMCol antioxidant moiety alone. PMCol has largely been investigated for its antioxidant activity associated with being the antioxidant moiety of vitamin E. For example, the antioxidant potency of PMCol was shown to be similar to that of -tocopherol in vitro (29). In general, -tocopherol plasma levels range between 5 and 30 µM (30), well within the range of antiandrogenic activity observed by PMCol in the current study.
Due to the high lipophilicity of vitamin E, it is difficult to assess its antiandrogenic activity by cell culture analysis. However, we can speculate that due to the presence of the highly lipophilic phytyl chain, the subcellular distribution of vitamin E would limit its direct interaction with the AR, which resides in more aqueous subcellular compartments such as the cytoplasm and nucleus. Vitamin E can be metabolized to derivatives with greater water solubility, such as carboxyethylhydroxychroman (7, 31), which are structurally similar to PMCol and may have greater water solubility and a distinct cellular bioavailability compared with vitamin E. Thus, we hypothesize that metabolites of vitamin E may contact the AR in vivo and have antiandrogenic activity, analogous to that produced by PMCol in human prostate carcinoma cells."
"...Importantly, the antiandrogenic activity of PMCol poses the possibility that the prostate cancer-preventive activity of vitamin E may be due, in part, to antiandrogenic effects of vitamin E or metabolites of vitamin E in the prostate. Currently, over 30,000 men die from prostate cancer each year in the United States (4). The prevention of prostate cancer through the action of dietary antiandrogens, such as vitamin E or its derivatives, may offer one means of reducing the devastation produced by this disease."