TY - JOUR
T1 - Vitamin E suppresses telomerase activity in ovarian cancer cells
AU - Bermudez, Yira
AU - Ahmadi, Shirrin
AU - Lowell, Nancy E.
AU - Kruk, Patricia A.
N1 - Funding Information:
This work was supported, in part, by US Army Department of Defense grant #DAMD17-02-0670 (Project #2) to PAK.
PY - 2007
Y1 - 2007
N2 - 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.
AB - 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.
KW - Telomerase inhibition
KW - Vitamin E acetate
KW - hTERT
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U2 - 10.1016/j.cdp.2006.12.002
DO - 10.1016/j.cdp.2006.12.002
M3 - Article
C2 - 17335992
AN - SCOPUS:34247623040
SN - 0361-090X
VL - 31
SP - 119
EP - 128
JO - Cancer detection and prevention
JF - Cancer detection and prevention
IS - 2
ER -