Journal of Microbiology and Biotechnology

The Korean Society for Microbiology and Biotechnology (한국미생물·생명공학회)
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Inhibition of Cell-Cycle Progression in Human Promyelocytic Leukemia HL-60 Cells by MCS-C2, Novel Cyclin-Dependent Kinase Inhibitor

  • Kim, Min-Kyoung (Department of Medical Genetics and Institute of Biomedical Science, College of Medicine, Hanyang University) ;
  • Cho, Youl-Hee (Department of Medical Genetics and Institute of Biomedical Science, College of Medicine, Hanyang University) ;
  • Kim, Jung-Mogg (Department of Microbiology, College of Medicine, Hanyang University) ;
  • Chun, Moon-Woo (College of Pharmacy, Seoul National University) ;
  • Lee, Seung-Ki (College of Pharmacy, Seoul National University) ;
  • Lim, Yoong-Ho (Bio/Molecular Informatics Center and Department of Applied Biology and Chemistry, Konkuk University) ;
  • Lee, Chul-Hoon (Department of Medical Genetics and Institute of Biomedical Science, College of Medicine, Hanyang University)
  • Published : 2003.08.01
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Abstract

To elucidate the action mechanism of MCS-C2, a novel analogue of toyocamycin and sangivamycin, its effect on the expression of cell cycle-related proteins in the human myelocytic leukemia cell line HL-60 was examined using Western blotting and a flow cytometric analysis. MCS-C2, a selective inhibitor of cyclin-dependent kinases, was found to inhibit cell growth in a time- and dose-dependent manner, and inhibits cell cycle progression by inducing the arrest at G1 and G2/M phases, in HL-60 cells. The flow cytometric analysis revealed an appreciable arrest of cells in the G2/M phase of the cell cycle after treatment with MCS-C2. The HL-60 cell population increased gradually from 13% at 0 h, to 28% at 12 h in the G2/M phase, after exposure to $2{\;}\mu\textrm{M}$ MCS-C2. Furthermore, Western blot analysis demonstrated that MCS-C2 induced the cell cycle arrest at G1 phase through the inhibition of pRb phosphorylation. Hypophosphorylated pRb accumulated after treatment with $5{\;}\mu\textrm{M}$ MCS-C2 for 12 h, whereas, the level of hyperphosphorylated pRb was reduced. Thus, treatment of the cell with MCS-C2 suppressed the hyperphosphorylated form of pRb with a commensurate increase in the hypophosphorylated form.

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