Vitamin E suppresses telomerase activity in ovarian cancer cells

Abstract 

Background: Dietary factors influence tumor formation and progression. Vitamin E is a dietary anti-oxidant capable of eliminating free radical damage, inducing apoptosis and decreasing oncogene expression. Therefore, Vitamin E may be a strong candidate for cancer prevention and/or chemotherapeutic intervention. Since telomerase, a ribonucleoprotein uniquely expressed in over 95% of cancers, plays an important role in cellular immortalization, cell growth and tumor progression, the present study investigated the effects of Vitamin E on telomerase activity in human ovarian cancer. Methods: Normal and malignant ovarian surface epithelial (OSE) cells were cultured with and without d-alpha tocopheryl acetate (Vitamin E). MTS and Western immunoblot assays were used to examine the effect of Vitamin E on cell growth, survival and cytotoxicity. PCR-ELISA, RT-PCR and luciferase reporter assays were performed to determine the effect of Vitamin E on telomerase activity. Results: Vitamin E suppressed endogenous telomerase activity in ovarian cancer cells, but had no similar effects in telomerase-negative normal OSE cells. Vitamin E also reduced hTERT-mRNA transcript levels and reduced hTERT promoter activity maximally targeting the −976 to −578bp promoter regions. In addition, Vitamin E improved cisplatin-mediated cytotoxicity as evidenced by reduced cancer cell growth and increased cleaved caspase 3 activity. In contrast, Vitamin E protected telomerase-negative OSE cells from cisplatin-mediated cytotoxicity as evidenced by decreased cleaved caspase 3 activity. Conclusion: Our data suggest that, by suppressing telomerase activity, Vitamin E may be an important protective agent against ovarian cancer cell growth as well as a potentially effective therapeutic adjuvant.

Abbreviations: CDDP, cisplatin, FBS, fetal bovine serum, GFP, green fluorescent protein, MTS, 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenol)-2-(4-sulfophenyl)-2H-tetrazolium, OSE, ovarian surface epithelial, PCR-ELISA, polymerase chain reaction enzyme-linked immunosorbent, PMS, phenazine methosulfate, α-TEA, 2,5,7,8-tetramethyl-2R-(4R,8R,12-trimethyltridecyl)-chroman-6-yloxyacetic acid, TRAP, telomere repeat amplification protocol, T-TBS, tris buffered saline plus 0.1% Tween-20, Vitamin E, d-alpha tocopheryl acetate

Keywords: Vitamin E acetate, Telomerase inhibition, hTERT