G1 phase arrest of the cell cycle by a ginseng metabolite, compound K, in U937 human monocytic leukamia cells.
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.
Kang
Kyoung Ah
KA
Department of Biochemistry, College of Medicine and Applied Radiological Science Research Institute, Cheju National University, 66 Jejudaehakno, Jeju-si 690-756 Korea.
Kim
Yeong Wan
YW
Kim
Seung Uk
SU
Chae
Sungwook
S
Koh
Young Sang
YS
Kim
Hee Sun
HS
Choo
Min Kyung
MK
Kim
Dong Hyun
DH
Hyun
Jin Won
JW
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
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