Abstract
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.
MeSH terms
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Anthracenes / pharmacology
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Apoptosis*
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Caspase 3
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Caspase Inhibitors
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Caspases / metabolism*
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Cell Proliferation / drug effects
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Cysteine Proteinase Inhibitors / pharmacology
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Diterpenes / pharmacology*
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Down-Regulation
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Enzyme Activation
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HeLa Cells
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Humans
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JNK Mitogen-Activated Protein Kinases / drug effects
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JNK Mitogen-Activated Protein Kinases / metabolism*
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Oligopeptides / pharmacology
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Protein Kinase Inhibitors / pharmacology
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Proto-Oncogene Proteins c-bcl-2 / metabolism
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Signal Transduction / drug effects*
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Up-Regulation
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bcl-2-Associated X Protein
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bcl-X Protein
Substances
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Anthracenes
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BAX protein, human
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BCL2L1 protein, human
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Caspase Inhibitors
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Cysteine Proteinase Inhibitors
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Diterpenes
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Oligopeptides
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Protein Kinase Inhibitors
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Proto-Oncogene Proteins c-bcl-2
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bcl-2-Associated X Protein
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bcl-X Protein
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benzoylcarbonyl-aspartyl-glutamyl-valyl-aspartyl-fluoromethyl ketone
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pyrazolanthrone
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pseudolaric acid B
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JNK Mitogen-Activated Protein Kinases
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CASP3 protein, human
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Caspase 3
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Caspases