Involvement of caspase-3 activation in squamocin-induced apoptosis in leukemia cell line HL-60.

Abstract	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 IC50 value of 0.17 microg/ml and induced apoptosis of HL-60 cells. Investigation of the mechanism of squamocin-induced 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.
Authors	Xiao-Feng Zhu, Zong-Chao Liu, Bin-Fen Xie, Zhi-Ming Li, Gong-Kan Feng, Hai-Hui Xie, Shu-Jun Wu, Ren-Zhou Yang, Xiao-Yi Wei, Yi-Xin Zeng
Journal	Life sciences (Life Sci) Vol. 70 Issue 11 Pg. 1259-69 (Feb 01 2002) ISSN: 0024-3205 [Print] Netherlands
PMID	11883704 (Publication Type: Journal Article)
Chemical References	Antineoplastic Agents, Phytogenic Caspase Inhibitors DNA, Neoplasm Furans Lactones Oligopeptides aspartyl-glutamyl-valyl-aspartal squamocin Poly(ADP-ribose) Polymerases CASP3 protein, human Caspase 3 Caspases
Topics	Antineoplastic Agents, Phytogenic (pharmacology) Apoptosis (drug effects) Caspase 3 Caspase Inhibitors Caspases (metabolism) Cell Division (drug effects) Cell Nucleus (drug effects, pathology) DNA, Neoplasm (analysis) Dose-Response Relationship, Drug Enzyme Activation (drug effects) Furans (pharmacology) HL-60 Cells (drug effects, enzymology, pathology) Humans Lactones (pharmacology) Oligopeptides (pharmacology) Poly(ADP-ribose) Polymerases (metabolism)

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