Telomerase activity is not related to apoptosis in leukemic cell lines.
Any deregulation of apoptosis or an escape from cellular senescence will drive the cells to neoplasia. It remains unclear whether there is a direct linkage between apoptosis and telomerase activity particularly in transformed cell lines. In the present study, we investigated the telomerase activities in three leukemic cell lines (HL-60, U937 and K562) after treating these cells with various doses of antitumor drugs, puromycin or actinomycin D (ActD). Our results showed that HL-60 cells underwent apoptosis rapidly when treated with either 20 microg/ml of puromycin or 5 microg/ml of Act D with more than 60% of the cells becoming apoptotic at 6 hrs and almost 100% at 12 hrs. But telomerase activity analyzed by TRAP assay in these apoptotic cells remained unchanged as compared with the untreated control cells suggesting that whether the cells were apoptotic or not, it had no effect on telomerase activity. However, if lower dosages of the drugs were used, that is, 0.5-1.5 microg/ml of puromycin or 0.01-0.5 microg/ml of Act D, a decrease in telomerase activity was observed at 24-48 hrs, and was completely undetectable at 72 hrs. This decrease in telomerase activity was dose- and time-dependent. The suppression of telomerase activity by low doses of these two drugs is probably due to the inhibitory effect of the drugs on protein translation or RNA transcription rather than direct inhibition of the telomerase activity. Flow cytometry analysis of the cell cycle of the drug-treated cells showed that these drugs unselectively induced apoptosis at all phases of the cell cycle and was unrelated to the changes in telomerase activity. Similar results were observed in U937 and K562 cells except that K562 cells underwent apoptosis more slowly than the former two cell lines.
Zhang
J X
JX
Department of Physiology, Faculty of Medicine, The University of Hong Kong, China.
Zhang
Z K
ZK
Sheng
H P
HP
Tsao
S W
SW
Loh
T T
TT
D000964:Antimetabolites, Antineoplastic / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology*; D053938:DNA Fragmentation / Q000187:drug effects; D003609:Dactinomycin / Q000494:pharmacology; D015536:Down-Regulation / Q000187:drug effects; D005434:Flow Cytometry; D018922:HL-60 Cells; D006801:Humans; D020014:K562 Cells; D007938:Leukemia / Q000201:enzymology / Q000473:pathology*; D011691:Puromycin / Q000494:pharmacology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D019098:Telomerase / Q000378:metabolism*; D020298:U937 Cells
D000964:Antimetabolites, Antineoplastic; D003609:Dactinomycin; D011691:Puromycin; D019098:Telomerase