title: G1 phase arrest of the cell cycle by a ginseng metabolite, compound K, in U937 human monocytic leukamia cells.
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.
authors.affiliation: Department of Biochemistry, College of Medicine and Applied Radiological Science Research Institute, Cheju National University, 66 Jejudaehakno, Jeju-si 690-756 Korea.
authors.forename: Kyoung Ah
authors.initials: KA
authors.lastname: Kang
authors.forename: Yeong Wan
authors.initials: YW
authors.lastname: Kim
authors.forename: Seung Uk
authors.initials: SU
authors.lastname: Kim
authors.forename: Sungwook
authors.initials: S
authors.lastname: Chae
authors.forename: Young Sang
authors.initials: YS
authors.lastname: Koh
authors.forename: Hee Sun
authors.initials: HS
authors.lastname: Kim
authors.forename: Min Kyung
authors.initials: MK
authors.lastname: Choo
authors.forename: Dong Hyun
authors.initials: DH
authors.lastname: Kim
authors.forename: Jin Won
authors.initials: JW
authors.lastname: Hyun
mesh_terms: D056741:Cyclin D; D051358:Cyclin-Dependent Kinase 4; D018844:Cyclin-Dependent Kinases / Q000378:metabolism; D016213:Cyclins / Q000037:antagonists & inhibitors / Q000378:metabolism; D004591:Electrophoresis, Polyacrylamide Gel; D024202:Electrophoretic Mobility Shift Assay; D004789:Enzyme Activation; D005434:Flow Cytometry; D016193:G1 Phase / Q000187:drug effects*; D036145:Ginsenosides / Q000302:isolation & purification / Q000494:pharmacology*; D006801:Humans; D048055:Mitogen-Activated Protein Kinase 8 / Q000378:metabolism; D048056:Mitogen-Activated Protein Kinase 9 / Q000378:metabolism; D005894:Panax / Q000737:chemistry; D017346:Protein Serine-Threonine Kinases / Q000096:biosynthesis / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D018808:Transcription Factor AP-1 / Q000378:metabolism; D020298:U937 Cells / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D054462:p21-Activated Kinases
chemical_list: D056741:Cyclin D; D051358:Cyclin-Dependent Kinase 4; D018844:Cyclin-Dependent Kinases; D016213:Cyclins; D036145:Ginsenosides; D048055:Mitogen-Activated Protein Kinase 8; D048056:Mitogen-Activated Protein Kinase 9; D017346:Protein Serine-Threonine Kinases; D011518:Proto-Oncogene Proteins; D018808:Transcription Factor AP-1; D054462:p21-Activated Kinases; C112772:ginsenoside compound K; C515907:PAK2 protein, human; C495900:CDK4 protein, human