Pseudolaric acid B induces apoptosis via activation of c-Jun N-terminal kinase and caspase-3 in HeLa cells.
Pseudolaric acid B was isolated from Pseudolarix kaempferi Gordon (Pinaceae) and was evaluated for the anti-cancer effect in HeLa cells. We ob-served that pseudolaric acid B inhibited cell proliferation and induced apoptosis in a time- and dose-dependent manner. HeLa cells treated with pseudolaric acid B showed typical characteristics of apoptosis including the morphological changes and DNA fragmentation. JNK inhibitor, SP600125,markedly inhibited pseudolaric acid B-induced celldeath. In addition, Bcl-2 expression was down-regulated while Bax protein level was up-regulated.Caspase-3 inhibitor, z-DEVD-fmk, partially blocked pseudolaric acid B-induced cell death, and the expression of two classical caspase substrates,PARP and ICAD, were both decreased in a time-dependent manner, indicative of downstream cas-pase activation.
Gong
Xianfeng
X
China-Japan Research Institute of Medical Pharmaceutical Sciences, Department of Pharmacology, Shenyang Pharmaceutical University, China.
Wang
Minwei
M
Wu
Zhen
Z
Tashiro
Shin-ichi
S
Onodera
Satoshi
S
Ikejima
Takashi
T
D000873:Anthracenes / Q000494:pharmacology; D017209:Apoptosis; D053148:Caspase 3; D061945:Caspase Inhibitors; D020169:Caspases / Q000378:metabolism*; D049109:Cell Proliferation / Q000187:drug effects; D015853:Cysteine Proteinase Inhibitors / Q000494:pharmacology; D004224:Diterpenes / Q000494:pharmacology*; D015536:Down-Regulation; D004789:Enzyme Activation; D006367:HeLa Cells; D006801:Humans; D048031:JNK Mitogen-Activated Protein Kinases / Q000187:drug effects / Q000378:metabolism*; D009842:Oligopeptides / Q000494:pharmacology; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects*; D015854:Up-Regulation; D051028:bcl-2-Associated X Protein; D051020:bcl-X Protein
D000873:Anthracenes; C494826:BAX protein, human; C494811:BCL2L1 protein, human; D061945:Caspase Inhibitors; D015853:Cysteine Proteinase Inhibitors; D004224:Diterpenes; D009842:Oligopeptides; D047428:Protein Kinase Inhibitors; D019253:Proto-Oncogene Proteins c-bcl-2; D051028:bcl-2-Associated X Protein; D051020:bcl-X Protein; C110772:benzoylcarbonyl-aspartyl-glutamyl-valyl-aspartyl-fluoromethyl ketone; C432165:pyrazolanthrone; C058391:pseudolaric acid B; D048031:JNK Mitogen-Activated Protein Kinases; C505407:CASP3 protein, human; D053148:Caspase 3; D020169:Caspases