Development of a new Ca2+/calmodulin antagonist and its anti-proliferative activity against colorectal cancer cells

Joong Sup Shim, Jiyong Lee, Kyung Noo Kim, Ho Jeong Kwon

Research output: Contribution to journalArticle

17 Citations (Scopus)

Abstract

We previously identified a cellular target of a cell cycle inhibitor HBC as Ca2+/calmodulin (Ca2+/CaM) through chemical genetics approach. Using the mechanism-based drug design, we developed a new Ca2+/CaM antagonists based on the structure of HBC. The compound, (4-{3,5-bis-[2-(4-hydroxy-3-methoxy-phenyl)-vinyl]-4,5-dihydro-pyrazol-1-yl}-phenyl)-(4-methyl-piperazin-1-yl)-methanone (referred as HBCP), binds to Ca2+/CaM in vitro and inhibits the proliferation of HCT15 colon cancer cells. HBCP induced sustained phosphorylation of ERK1/2 and subsequently activated p21WAF1 expression in HCT15 cells. Moreover, HBCP reversibly induced the G0/G1 cell cycle arrest in the cells. These data demonstrate that HBCP is a new potent Ca2+/CaM antagonist and can be applied for CaM related therapeutic uses.

Original languageEnglish
Pages (from-to)747-751
Number of pages5
JournalBiochemical and Biophysical Research Communications
Volume359
Issue number3
DOIs
Publication statusPublished - 2007 Aug 3

All Science Journal Classification (ASJC) codes

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

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