G1 phase arrest of the cell cycle by a ginseng metabolite, compound K, in U937 human monocytic leukamia cells

Kyoung Ah Kang; Yeong Wan Kim; Seung Uk Kim; Sungwook Chae; Young Sang Koh; Hee Sun Kim; Min Kyung Choo; Dong Hyun Kim; Jin Won Hyun

doi:10.1007/BF02969359

G1 phase arrest of the cell cycle by a ginseng metabolite, compound K, in U937 human monocytic leukamia cells

Arch Pharm Res. 2005 Jun;28(6):685-90. doi: 10.1007/BF02969359.

Authors

Kyoung Ah Kang¹, Yeong Wan Kim, Seung Uk Kim, Sungwook Chae, Young Sang Koh, Hee Sun Kim, Min Kyung Choo, Dong Hyun Kim, Jin Won Hyun

Affiliation

¹ Department of Biochemistry, College of Medicine and Applied Radiological Science Research Institute, Cheju National University, 66 Jejudaehakno, Jeju-si 690-756 Korea.

PMID: 16042078
DOI: 10.1007/BF02969359

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

Comparative Study
Research Support, Non-U.S. Gov't

MeSH terms

Cyclin D
Cyclin-Dependent Kinase 4
Cyclin-Dependent Kinases / metabolism
Cyclins / antagonists & inhibitors
Cyclins / metabolism
Electrophoresis, Polyacrylamide Gel
Electrophoretic Mobility Shift Assay
Enzyme Activation
Flow Cytometry
G1 Phase / drug effects*
Ginsenosides / isolation & purification
Ginsenosides / pharmacology*
Humans
Mitogen-Activated Protein Kinase 8 / metabolism
Mitogen-Activated Protein Kinase 9 / metabolism
Panax* / chemistry
Protein Serine-Threonine Kinases / biosynthesis
Protein Serine-Threonine Kinases / metabolism
Proto-Oncogene Proteins / metabolism
Transcription Factor AP-1 / metabolism
U937 Cells / cytology
U937 Cells / drug effects*
U937 Cells / metabolism
p21-Activated Kinases

Substances

Cyclin D
Cyclins
Ginsenosides
Proto-Oncogene Proteins
Transcription Factor AP-1
ginsenoside M1
Mitogen-Activated Protein Kinase 9
PAK2 protein, human
Protein Serine-Threonine Kinases
p21-Activated Kinases
CDK4 protein, human
Cyclin-Dependent Kinase 4
Cyclin-Dependent Kinases
Mitogen-Activated Protein Kinase 8