Topotecan induces caspase-dependent apoptosis in HL-60 cells

AIM To gain insight into the biochemical mechanisms of Topotecan induced apoptosis in leukemia cells. METHODS The cytotoxic effect of Topotecan on HL 60 cells was measured by using MTT assay; Topotecan induced apoptosis in HL 60 cells was identified by morphological analysis, DNA agarose gel electropheresis and Annexin V FITC staining; correlation between Topotecan mediated apoptosis and caspase activation was investigated by caspase 8 or caspase 3 inhibitor. RESULTS After incubated with 0 1 μmol·L -1 TPT for 8,12 and 16 h, survival rate in HL 60 cells significantly reduced to 62%±12%( P 0 05), 43%±15%( P 0 05) and 32%±10%( P 0 05), respectively, and HL 60 cells, meanwhile, were broken down into apoptotic bodies and demonstrated ladder DNA formation and phosphatydilserine externalization; after exposure to Topotecan in combination with IETD fmk or DEVD CHO for 12 and 16 h, survival rates in HL 60 cells were remarkably raised to 77%±14%( P 0 05)?65%±16%( P 0 05) and 74%±12%( P 0 05)?60%±11%( P 0 05), and, in the meantime, formation of ladder DNA and apoptotic bodies was notably inhibited. CONCLUSION Topotecan is most potent in inducing apoptosis in HL 60 cells, which depends on activation of caspase 8 and caspase 3,consecutively.