期刊
CANCER DETECTION AND PREVENTION
卷 31, 期 2, 页码 119-128出版社
ELSEVIER SCI LTD
DOI: 10.1016/j.cdp.2006.12.002
关键词
vitamin E acetate; telomerase inhibition; hTERT
类别
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). NITS 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 -578 bp 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. (C) 2006 International Society for Preventive Oncology. Published by Elsevier Ltd. All rights reserved.
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