Down-regulation of telomerase activity by anticancer drugs in human ovarian cancer cells.
Maintenance of telomere length is crucial for survival of cells. Telomerase, an enzyme that is responsible for elongation of shortened telomeres, is active in human germ cells as well as most tumor tissues and experimentally immortalized cells. In contrast, most mature somatic cells in human tissues express undetectable or low telomerase activity, implying the existence of a stringent and negative regulatory mechanism. In this study we report the effects of anticancer drugs on telomerase activity in human cancer cells. In assaying for telomerase activity, we basically followed the original TRAP assay system, but with some modifications. A down-regulation of telomerase activity was found when cells of a human ovarian cancer cell line, A2780, were treated with;cis-diamminedichloroplatinum(II) (CDDP; cisplatin). However, down-regulation of telomerase activity was not found in cells of a cisplatin-resistant cell line, A2780CP, treated with cisplatin. On the other hand, telomerase activity in both the cell lines A2780 and A2780CP was reduced when A2780 or A2780CP was treated with adriamycin, an anthracycline antibiotic having a broad spectrum of antineoplastic activity. The different effects on the telomerase activity of the two types of anticancer drugs may be due the distinct chemical functions of these drugs. The present results may indicate a positive relationship between anticancer effects and down-regulation of telomerase activity by anticancer drugs.
Kunifuji
Yasumasa
Y
School of Health Sciences, University of Occupational and Environmental Health, Kitakyushu 807-8555, Japan. ykunifu@med.uoeh-u.ac.jp
Gotoh
Sadao
S
Abe
Tetsuya
T
Miura
Masayoshi
M
Karasaki
Yuji
Y
D000903:Antibiotics, Antineoplastic / Q000494:pharmacology; D000970:Antineoplastic Agents / Q000494:pharmacology*; D002470:Cell Survival / Q000187:drug effects; D002945:Cisplatin / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation / Q000187:drug effects*; D004317:Doxorubicin / Q000494:pharmacology; D005260:Female; D006801:Humans; D007770:L-Lactate Dehydrogenase / Q000096:biosynthesis; D010051:Ovarian Neoplasms / Q000188:drug therapy* / Q000201:enzymology* / Q000235:genetics; D019098:Telomerase / Q000096:biosynthesis* / Q000235:genetics; D013997:Time Factors; D014407:Tumor Cells, Cultured
D000903:Antibiotics, Antineoplastic; D000970:Antineoplastic Agents; D004317:Doxorubicin; D007770:L-Lactate Dehydrogenase; D019098:Telomerase; D002945:Cisplatin