title: 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.affiliation: Cancer Institute, Cancer Center, Sun Yat-sen University of Medical Sciences, Guangzhou, China.
authors.forename: Xiao-Feng
authors.initials: XF
authors.lastname: Zhu
authors.forename: Zong-Chao
authors.initials: ZC
authors.lastname: Liu
authors.forename: Bin-Fen
authors.initials: BF
authors.lastname: Xie
authors.forename: Zhi-Ming
authors.initials: ZM
authors.lastname: Li
authors.forename: Gong-Kan
authors.initials: GK
authors.lastname: Feng
authors.forename: Hai-Hui
authors.initials: HH
authors.lastname: Xie
authors.forename: Shu-Jun
authors.initials: SJ
authors.lastname: Wu
authors.forename: Ren-Zhou
authors.initials: RZ
authors.lastname: Yang
authors.forename: Xiao-Yi
authors.initials: XY
authors.lastname: Wei
authors.forename: Yi-Xin
authors.initials: YX
authors.lastname: Zeng
mesh_terms: D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D053148:Caspase 3; D061945:Caspase Inhibitors; D020169:Caspases / Q000378:metabolism*; D002455:Cell Division / Q000187:drug effects; D002467:Cell Nucleus / Q000187:drug effects / Q000473:pathology; D004273:DNA, Neoplasm / Q000032:analysis; D004305:Dose-Response Relationship, Drug; D004789:Enzyme Activation / Q000187:drug effects; D005663:Furans / Q000494:pharmacology*; D018922:HL-60 Cells / Q000187:drug effects* / Q000201:enzymology / Q000473:pathology; D006801:Humans; D007783:Lactones / Q000494:pharmacology*; D009842:Oligopeptides / Q000494:pharmacology; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D061945:Caspase Inhibitors; D004273:DNA, Neoplasm; D005663:Furans; D007783:Lactones; D009842:Oligopeptides; C108637:aspartyl-glutamyl-valyl-aspartal; C059660:squamocin; D011065:Poly(ADP-ribose) Polymerases; C505407:CASP3 protein, human; D053148:Caspase 3; D020169:Caspases