Antioxidants, such as
vitamin E, are being investigated for efficacy in
prostate cancer prevention. In this study, we show that the
antioxidant moiety of
vitamin E,
2,2,5,7,8-pentamethyl-6-chromanol (PMCol), has
antiandrogen activity in prostate
carcinoma cells. In the presence of PMCol, the
androgen-stimulated biphasic growth curve of LNCaP human prostate
carcinoma cells was shifted to the right. The PMCol-induced growth shift was similar to that produced by treatment with the pure
antiandrogen bicalutamide (i.e.,
Casodex), indicative of
androgen receptor (AR) antagonist activity. The concentration of PMCol used was below the concentration required to affect cell growth or viability in the absence of
androgen. Using an AR binding competition assay, PMCol was found to be a potent
antiandrogen in both LNCaP and LAPC4 cells, with an IC(50) of approximately 10 micro M against 1 nM
R1881 (
methyltrienolone; a stable,
synthetic androgen).
Prostate-specific antigen release from LNCaP cells produced by
androgen exposure with either 0.05 or 1.0 nM
R1881 was inhibited 100% and 80%, respectively, by 30 micro M PMCol. Also, PMCol inhibited
androgen-induced promoter activation in both LNCaP and LAPC4 cells. However, PMCol did not affect AR
protein levels, suggesting that the inhibitory effects of PMCol on androgenic pathways were not due to decreased expression of the AR. Therefore, growth modulation by the
antioxidant moiety of
vitamin E in
androgen-sensitive prostate
carcinoma cells is due, at least in part, to its potent antiandrogenic activity.