Involvement of caspase-3 activation in squamocin-induced apoptosis in leukemia cell line HL-60
Life Sciences 70(2002)1259-1269，-0001，（）：
Annonaceous acetogenins have potent antitumor effect in vitro and in vivo. Squamocin is one of the annonaceous acetogenins and has been reported to have antiproliferative effect on cancer cells. Our results from this study showed that squamocin inhibited proliferation of HL-60 cells with IC 50 value of 0.17 m g/ml and induced apoptosis of HL-60 cells. Investigation of the mechanism of squamocininduced apoptosis revealed that treatment of HL-60 cells with squamocin resulted in extensive nuclear condensation, DNA fragmentation, cleavage of the death substrate poly (ADP-ribose) polymerase (PARP) and induction of caspase-3 activity. Pretreatment of HL-60 cells with caspase-3 specific inhibitor DEVD-CHO prevented squamocin-induced DNA fragmentation, PARP cleavage and cell death. The expression levels of protein bcl-2, bax have no change in response to squamocin treatment in HL-60 cells, whereas stress-activated protein kinase (SAPK/JNK) was activated after treatment with squamocin in HL-60 cells. These results suggest that apoptosis of HL-60 cells induced by squamocin requires caspase-3 activation and is related to SAPK activation. © 2002 Elsevier Science Inc. All rights reserved.