Involvement of caspase-3 activation in squamocin-induced apoptosis in leukemia cell line HL-60.
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.
Zhu
Xiao-Feng
XF
Cancer Institute, Cancer Center, Sun Yat-sen University of Medical Sciences, Guangzhou, China.
Liu
Zong-Chao
ZC
Xie
Bin-Fen
BF
Li
Zhi-Ming
ZM
Feng
Gong-Kan
GK
Xie
Hai-Hui
HH
Wu
Shu-Jun
SJ
Yang
Ren-Zhou
RZ
Wei
Xiao-Yi
XY
Zeng
Yi-Xin
YX
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
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