The telomere and
telomerase have been suggested as targets for anticancer drug discovery. However, the mechanisms by which conventional anticancer drugs affect these targets are currently unclear. The novel
topoisomerase II inhibitor,
salvicine, suppresses
telomerase activity in
leukemia HL-60 cells. To further determine whether this activity of
salvicine is specific to the hematological
tumor and distinct from those of other conventional
anticancer agents, we studied its effects on telomere and
telomerase in a solid lung
carcinoma cell line, A549. Differences in
telomerase inhibition and telomere erosion were observed between salvcine and other
anticancer agents. All
anticancer agents (except
adriamycin) induced shortening of the telomere, which was identified independent of replication, but only
salvicine inhibited
telomerase activity in A549 cells under conditions of high concentration and short-term exposure. At the low concentration and long-term exposure mode, all the tested
anticancer agents shortened the telomere and inhibited
telomerase activity in the same cell line. Notably,
salvicine inhibited
telomerase activity more severely than the other agents examined. Moreover, the compound inhibited
telomerase activity in A549 cells indirectly in a concentration- and time-dependent manner.
Salvicine did not affect the expression of hTERT, hTP1, and hTR
mRNA in A549 cells following 4 h of exposure.
Okadaic acid protected
telomerase from inhibition by
salvicine. These results indicate specificity of
salvicine and diversity of
anticancer agents in the mechanism of interference with
telomerase and the telomere system. Our data should be helpful for designing the study in the development of agents acting on telomere and/or
telomerase.