Differential retention of α‐vitamin E is correlated with its transporter gene expression and growth inhibition efficacy in prostate cancer cells

BACKGROUND Epidemiological studies showed Vit E has protective effects against prostate cancer (PCa). Interestingly, different prostate cancer cells have different sensitivity to α‐Vit E or VES treatment. The goal of this study is to determine whether cellular Vit E bioavailability and its transport proteins are important contributing factors. METHODS α‐Vit E and its ester form, VES, were used to treat prostate cancer LNCaP, PC3, and DU145 cells, and their growth rates were determined by MTT assay. Cellular levels of Vit E were quantified using HPLC as the index of bioavailability. The expression levels of Vit E transport proteins were determined by real‐time PCR. RESULTS Among these PCa cells, only LNCaP cells were sensitive to 20 µM α‐Vit E treatment, while both LNCaP and PC3 cells were sensitive to 20 µM VES treatment. Coordinately, cellular levels of α‐Vit E and VES positively correlated to their inhibitory effects. Further study found expression levels of Vit E transport proteins, including tocopherol associated protein (TAP), scavenger receptor class B type I (SR‐BI), α‐tocopherol transfer protein (TTP), and ATP binding cassette transporter A1 (ABCA1), were different in various PCa cells, which may contribute to cellular Vit E bioavailability. This notion is further supported by the findings that overexpression or knockdown of TTP could coordinately alter cellular α‐Vit E levels in PCa cells. CONCLUSION Antiproliferative efficacy of α‐Vit E is correlated with its cellular bioavailability in PCa cells. Modulating the expression of the efflux or influx transporters could sensitize the growth inhibition efficacy of Vit E in prostate cancer cells. Prostate 67: 463–471, 2007. © 2007 Wiley‐Liss, Inc.