Up-regulation of
telomerase activity is associated with immortalization and unlimited cell division in most
cancer cells. Therefore,
telomerase represents a particularly attractive target for anticancer
therapy. Recent reports have suggested that
beta-lapachone (LAPA), the product of the South American Tabebuia avellanedae tree, inhibits growth of
tumor cells. However, the underlying relationship between
telomerase activity and apoptosis in response to LAPA exposure in
leukemia cells remains poorly understood. In this study, we confirmed that LAPA treatment induces direct cytotoxicity in human
leukemia cells (U937, K562, HL60, and THP-1) through activation of
caspase-3 and subsequent cleavage of
poly(ADP-ribose) polymerase. The observed induction of cell death was associated with decreased
telomerase activity, which was ascribed to down-regulation of
telomerase reverse transcriptase. Additionally, overexpression of anti-apoptotic Bcl-2 could not overcome the induction of apoptosis or the decreased
telomerase activity in response to treatment of U937 cells with LAPA. We conclude that LAPA has a direct cytotoxic effect and the loss of
telomerase activity in
leukemia cells.