Effect of all-trans retinoic acid on telomerase activity in ovarian cancer cells.
Vitamin A is an essential nutrient important for growth, vision, embryonic development, immune response and reproduction. Various retinoids have been shown to be effective chemotherapeutic and chemopreventive agents for a number of human cancers. Telomeres are nucleoprotein structures found at the end of chromosomes. During cellular division, the telomeres in normal cells shorten progressively and thus, function as a "molecular clock". Telomerase is a ribonucleoprotein complex that extends and maintains telomeres. Activation of telomerase is required for cells to overcome proliferative crisis. Telomerase activation is observed in 90% of human cancers, but not in normal somatic cells. We examined the role of telomerase in mediating the growth suppression of ovarian carcinoma cells by all-trans-retinoic acid (ATRA). Using a number of cell lines with varying levels of growth sensitivity to ATRA, we found that cells that exhibit ATRA-dependant suppression of growth also contained significantly reduced telomerase activity. We also observed a reduction in expression of the telomerase components, hTERT and hTR in ATRA treated ovarian carcinoma cells. Our results suggest that one mechanism by which ATRA acid inhibits cancer cell growth is by suppressing telomerase activity, thereby pushing cells to proliferative crisis.
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Dept of Microbiology and Immunology, Temple University School of Medicine, Philadelphia, PA 19140, USA.
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D000970:Antineoplastic Agents / Q000494:pharmacology*; D020134:Catalytic Domain; D004268:DNA-Binding Proteins; D015536:Down-Regulation / Q000187:drug effects*; D005260:Female; D006801:Humans; D010051:Ovarian Neoplasms / Q000201:enzymology* / Q000473:pathology; D012313:RNA; D062085:RNA, Long Noncoding; D012333:RNA, Messenger / Q000235:genetics; D012334:RNA, Neoplasm / Q000235:genetics; D022661:RNA, Untranslated / Q000037:antagonists & inhibitors / Q000235:genetics; D019098:Telomerase / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism*; D014212:Tretinoin / Q000494:pharmacology*; D014407:Tumor Cells, Cultured
D000970:Antineoplastic Agents; D004268:DNA-Binding Proteins; D062085:RNA, Long Noncoding; D012333:RNA, Messenger; D012334:RNA, Neoplasm; D022661:RNA, Untranslated; C422952:telomerase RNA; D014212:Tretinoin; D012313:RNA; D019098:Telomerase