Abstract
We recently reported that the ginseng saponin metabolite, compound K (20-O-beta-D-glucopyranosyl-20(S)-protopanaxadiol, IH901), inhibits the growth of U937 cells through caspase-dependent apoptosis pathway. In this study, we further characterized the effects of compound K on U937 cells and found that, in addition to apoptosis, compound K induced the arrest of the G1 phase. The compound K treated U937 cells showed increased p21 expression; an inhibitory protein of cyclin-cdk complex. The up-regulation of p21 was followed by the inactivation of cyclin D and the cdk4 protein, which act at the early G1 phase, and cyclin E, which acts at the late G1 phase. Furthermore, compound K induced the activation of JNK and the transcription factor AP-1, which is a downstream target of JNK. These findings suggest that the up-regulation of p21 and activation of JNK in the compound K treated cells contribute to the arrest of the G1 phase.
Publication types
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Comparative Study
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Research Support, Non-U.S. Gov't
MeSH terms
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Cyclin D
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Cyclin-Dependent Kinase 4
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Cyclin-Dependent Kinases / metabolism
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Cyclins / antagonists & inhibitors
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Cyclins / metabolism
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Electrophoresis, Polyacrylamide Gel
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Electrophoretic Mobility Shift Assay
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Enzyme Activation
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Flow Cytometry
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G1 Phase / drug effects*
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Ginsenosides / isolation & purification
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Ginsenosides / pharmacology*
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Humans
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Mitogen-Activated Protein Kinase 8 / metabolism
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Mitogen-Activated Protein Kinase 9 / metabolism
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Panax* / chemistry
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Protein Serine-Threonine Kinases / biosynthesis
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Protein Serine-Threonine Kinases / metabolism
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Proto-Oncogene Proteins / metabolism
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Transcription Factor AP-1 / metabolism
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U937 Cells / cytology
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U937 Cells / drug effects*
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U937 Cells / metabolism
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p21-Activated Kinases
Substances
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Cyclin D
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Cyclins
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Ginsenosides
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Proto-Oncogene Proteins
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Transcription Factor AP-1
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ginsenoside M1
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Mitogen-Activated Protein Kinase 9
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PAK2 protein, human
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Protein Serine-Threonine Kinases
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p21-Activated Kinases
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CDK4 protein, human
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Cyclin-Dependent Kinase 4
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Cyclin-Dependent Kinases
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Mitogen-Activated Protein Kinase 8