Activation of caspases-3/7 is dispensable for idarubicin-induced apoptotic DNA fragmentation in human leukemia cells.
Idarubicin (IDA) is a 4-demethoxy-anthracycline analogue of daunorubicin (DNR). IDA has been recognized as a potent anti-leukemic agent. However, the molecular mechanism of IDA-induced cell death remains unclear. In the present study, we investigated the activity of IDA to induce apoptosis in human leukemia HL-60 and Jurkat cells, and studied its relationship with activation of caspases-3/7. IDA induced apoptotic DNA fragmentation in a time- and dose-dependent manner. The kinetics of apoptotic DNA fragmentation induced by IDA was well correlated with that of caspase-3/7 activation. We examined the effect of caspase-3/7 inhibitor Ac-DEVD-CHO on IDA-induced apoptosis in HL-60 and Jurkat cells. Ac-DEVD-CHO abolished IDA-induced caspases-3/7 activation in both cell lines. We have also found that L-carnitine can inhibit recombinant caspase-3 activity in vitro. L-carnitine treatment prevented IDA-induced caspases-3/7 activation in both cell lines in a dose-dependent manner. However, neither Ac-DEVD-CHO nor L-carnitine inhibited IDA-induced apoptotic internucleosomal DNA fragmentation in HL-60 or Jurkat cells. These data suggest that caspase-3/7 may be dispensable for idarubicin-induced internucleosomal DNA cleavage during apoptosis in human leukemia cells.
Qi
She-Ning
SN
First Department of Internal Medicine, Fukui Medical University, Matsuoka, Fukui, Japan.
Yoshida
Akira
A
Ueda
Takanori
T
D000970:Antineoplastic Agents / Q000633:toxicity*; D017209:Apoptosis / Q000187:drug effects; D053148:Caspase 3; D053179:Caspase 7; D020169:Caspases / Q000378:metabolism*; D053938:DNA Fragmentation / Q000187:drug effects*; D004789:Enzyme Activation; D018922:HL-60 Cells; D006801:Humans; D015255:Idarubicin / Q000633:toxicity*; D019169:Jurkat Cells; D007700:Kinetics; D007938:Leukemia; D015842:Serine Proteinase Inhibitors / Q000494:pharmacology; D014407:Tumor Cells, Cultured
D000970:Antineoplastic Agents; D015842:Serine Proteinase Inhibitors; C505407:CASP3 protein, human; C505520:CASP7 protein, human; D053148:Caspase 3; D053179:Caspase 7; D020169:Caspases; D015255:Idarubicin