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.

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