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

• Published in: Archives of pharmacal research 2005, 28(6), , pp.685-690
• Main Authors: Kang, Kyoung Ah, Kim, Yeong Wan, Kim, Seung Uk, Chae, Sungwook, Koh, Young Sang, Kim, Hee Sun, Choo, Min Kyung, Kim, Dong Hyun, Hyun, Jin Won
• Format: Article
• Language: English
• Subjects: apoptosis; cell cycle checkpoints; Cyclin D; Cyclin-Dependent Kinase 4; Cyclin-Dependent Kinases - metabolism; cyclins; 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; interphase; metabolites; mitogen-activated protein kinase; Mitogen-Activated Protein Kinase 8 - metabolism; Mitogen-Activated Protein Kinase 9 - metabolism; p21-Activated Kinases; Panax; Panax - chemistry; Protein-Serine-Threonine Kinases - biosynthesis; Protein-Serine-Threonine Kinases - metabolism; Proto-Oncogene Proteins - metabolism; saponins; Transcription Factor AP-1 - metabolism; transcription factors; U937 Cells - cytology; U937 Cells - drug effects; U937 Cells - metabolism; 약학
• ISSN: 0253-6269; 1976-3786
• DOI: 10.1007/bf02969359

We recently reported that the ginseng saponin metabolite, compound K (20-O-β-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.