title: 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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Pathology and Cell Biology, University of South Florida, 12901 Bruce B. Downs Boulevard, Tampa, FL 33612, USA.
authors.forename: Yira
authors.initials: Y
authors.lastname: Bermudez
authors.forename: Shirrin
authors.initials: S
authors.lastname: Ahmadi
authors.forename: Nancy E
authors.initials: NE
authors.lastname: Lowell
authors.forename: Patricia A
authors.initials: PA
authors.lastname: Kruk
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology; D000975:Antioxidants / Q000494:pharmacology*; D015153:Blotting, Western; D053148:Caspase 3 / Q000378:metabolism; D049109:Cell Proliferation / Q000187:drug effects; D002945:Cisplatin / Q000494:pharmacology; D004591:Electrophoresis, Polyacrylamide Gel; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D010051:Ovarian Neoplasms / Q000201:enzymology* / Q000235:genetics / Q000473:pathology; D011401:Promoter Regions, Genetic / Q000235:genetics; D012333:RNA, Messenger / Q000378:metabolism; D012334:RNA, Neoplasm / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D019098:Telomerase / Q000037:antagonists & inhibitors* / Q000235:genetics; D014407:Tumor Cells, Cultured / Q000187:drug effects; D014810:Vitamin E / Q000494:pharmacology*
chemical_list: D000970:Antineoplastic Agents; D000975:Antioxidants; D012333:RNA, Messenger; D012334:RNA, Neoplasm; D014810:Vitamin E; C509186:TERT protein, human; D019098:Telomerase; D053148:Caspase 3; D002945:Cisplatin