Cytostatic concentrations of anticancer agents do not affect telomerase activity of leukaemic cells in vitro.
Telomerase, the enzyme that maintains the ends of linear eukaryotic chromosomes, is more active in the majority of malignant tumours than in normal somatic cells. Telomerase plays a key role in the maintenance of chromosomal stability in tumours, but it still remains unknown whether anticancer agents can inhibit telomerase activity. In this study, we evaluated the effect of various anticancer agents (etoposide, cisplatin, irinotecan, mitomycin C and daunorubicin) on the telomerase activity of three human haematopoietic cancer cell lines (Daudi, K562 and U937). A decrease of telomerase activity was not observed in cells treated with IC50 doses of the drugs, except for irinotecan-treated Daudi cells and daunorubicin- and irinotecan-treated U937 cells. Propidium iodide staining disclosed that the cells with decreased telomerase activity were severely damaged. U937 cells exposed to 5 microM (IC90) etoposide showed three different stages of cell viability during treatment. Apoptotic cells with an intact plasma membrane still maintained high telomerase activity, while cells with plasma membrane damage lost telomerase activity. The mRNA of the telomerase catalytic subunit (hTERT) showed a decrease in expression along with the decline of telomerase activity. These results indicate that the concentrations of drugs resulting in cytostatic effects on cells do not affect telomerase activity.
Akiyama
M
M
Department of Paediatrics, Jikei University School of Medicine, Tokyo, Japan.
Horiguchi-Yamada
J
J
Saito
S
S
Hoshi
Y
Y
Yamada
O
O
Mizoguchi
H
H
Yamada
H
H
D000970:Antineoplastic Agents / Q000627:therapeutic use*; D017209:Apoptosis; D004268:DNA-Binding Proteins; D006801:Humans; D007938:Leukemia / Q000188:drug therapy / Q000201:enzymology* / Q000473:pathology; D008223:Lymphoma / Q000188:drug therapy / Q000201:enzymology* / Q000473:pathology; D009363:Neoplasm Proteins / Q000037:antagonists & inhibitors* / Q000378:metabolism; D012313:RNA; D012333:RNA, Messenger / Q000378:metabolism; D012334:RNA, Neoplasm / Q000378:metabolism; D019098:Telomerase / Q000037:antagonists & inhibitors* / Q000378:metabolism; D014407:Tumor Cells, Cultured
D000970:Antineoplastic Agents; D004268:DNA-Binding Proteins; D009363:Neoplasm Proteins; D012333:RNA, Messenger; D012334:RNA, Neoplasm; C422952:telomerase RNA; D012313:RNA; D019098:Telomerase