Alpha-tocopherylquinone, the major oxidation product of vitamin E, selectively decreases androgenic activity, growth, and viability of prostate cancer cells.

A83

Results from epidemiological studies indicate that smoking and supplemental vitamin E (VE) may prevent prostate cancer. The mechanism for the combined action of smoking and supplemental VE on prostate cancer prevention is unknown. Chronic smoking produces a physiologic state of oxidative stress. The major oxidation product of VE is alpha-tocopherylquinone (ATQ), which is chemically distinct from VE. ATQ and VE were compared for their effects on prostate cancer cell growth, cell death, and on measures of androgenic activity in the LNCaP and PC3 human prostate carcinoma cell lines. ATQ produced a dose-dependent decrease in LNCaP growth, with a 26%, 36%, and 47% decrease in cell growth observed with physiologically relevant levels of 10, 20, and 30 μM, respectively, over 4 days. In contrast, treatment with VE up to 50 μM did not affect LNCaP growth over 4 days. Interestingly, neither ATQ nor VE significantly affected the growth of the androgen-independent PC3 cell line; whereas ATQ, but not VE, treatment resulted in 100% cell death in PC3 cells after reaching confluence for 48 hours. ATQ selectively inhibited androgen responsiveness in LNCaP cells compared to VE. For example, 25 μM ATQ inhibited androgen-induced expression from androgen-driven reporter vectors, whereas 25 μM VE had no effect. Similarly, ATQ significantly inhibited the androgen-induced expression of prostate specific antigen. In contrast, levels of VE up to 50 μM did not affect androgenic responses. LNCaP cells treated with 25 μM ATQ produced a 4-fold decrease in androgen receptor protein levels that was not observed following treatment with VE. A 2-fold decrease in androgen receptor mRNA was observed after ATQ treatment. In summary, ATQ, but not VE, was found to decrease growth, viability, and androgenic activity of human prostate cancer cells that may, in part, account for the prostate cancer preventive properties of concurrent smoking and supplemental VE. These observations will assist the development of effective VE-based strategies for prostate cancer prevention that do not necessitate smoking.