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

Department of Urology and Pathology, University of Rochester, Rochester, New York 14642, USA.
The Prostate (Impact Factor: 3.57). 04/2007; 67(5):463-71. DOI: 10.1002/pros.20517
Source: PubMed


Epidemiological studies showed Vit E has protective effects against prostate cancer (PCa). Interestingly, different prostate cancer cells have different sensitivity to alpha-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.
alpha-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.
Among these PCa cells, only LNCaP cells were sensitive to 20 microM alpha-Vit E treatment, while both LNCaP and PC3 cells were sensitive to 20 microM VES treatment. Coordinately, cellular levels of alpha-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), alpha-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 alpha-Vit E levels in PCa cells.
Antiproliferative efficacy of alpha-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.

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    • "For example , prostate cancer DU145 cells are less sensitive to 20‐mM a‐vitamin E or VES treatment. Consistently, the cellular amount of a‐vitamin E and VES in DU145 cells is much lower compared to that in other prostate cancer cells after a‐vitamin E/VES treatment (Ni et al., 2007). Therefore, the cell's uptake eYcacy might be one of the factors contributing to the growth inhibitory eYcacy of a‐vitamin E and VES. "

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