Telmerase activity is not related to apoptosis in leukemic cell lines

Any deregulation of apoptosis or an escape from cellular senescence will dr ive the cells to neoplasia. It remains unclear whether there is a direct li nkage between apoptosis and telomerase activity particularly in transformed cell lines. In the present study, we investigated the telomerase activitie s in three leukemic cell lines (HL-60, U937 and K562) after treating these cells with various doses of antitumor drugs, puromycin or actinomycin D (Ac t D). Our results showed that HL-60 cells underwent apoptosis rapidly when treated with either 20 mu g/ml of puromycin or 5 mu g/ml of Act D with more than 60% of the cells becoming apoptotic at 6 hrs and almost 100% at 12 hr s. 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 telomeras e activity. However, if lower dosages of the drugs were used, that is, 0.5- 1.5 mu g/ml of puromycin or 0.01-0.5 mu g/ml of Act D, a decrease in telome rase 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 o r RNA transcription rather than direct inhibition of the telomerase activit y. Flow cytometry analysis of the cell cycle of the drug-treated cells show ed that these drugs unselectively induced apoptosis at all phases of the ce ll cycle and was unrelated to the changes in telomerase activity. Similar r esults were observed in U937 and K562 cells except that K562 cells underwen t apoptosis more slowly than the former two cell lines.