Vitamin E suppresses telomerase activity in ovarian cancer cells

Yira Bermudez, Shirrin Ahmadi, Nancy E. Lowell, Patricia A. Kruk

Research output: Contribution to journalArticle

26 Scopus citations

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 -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.

Original languageEnglish (US)
Pages (from-to)119-128
Number of pages10
JournalCancer detection and prevention
Volume31
Issue number2
DOIs
StatePublished - May 4 2007

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Keywords

  • Telomerase inhibition
  • Vitamin E acetate
  • hTERT

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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