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Abstract Title:

A new curcumin derivative, HBC, interferes with the cell cycle progression of colon cancer cells via antagonization of the Ca2+/calmodulin function.

Abstract Source:

Chem Biol. 2004 Oct;11(10):1455-63. PMID: 15489172

Abstract Author(s):

Joong Sup Shim, Jiyong Lee, Hyun-Ju Park, So-Jung Park, Ho Jeong Kwon

Article Affiliation:

Chemical Genomics National Research Laboratory, Department of Bioscience and Biotechnology, Institute of Bioscience, Sejong University, Seoul 143-747, Korea.

Abstract:

HBC (4-[3,5-Bis-[2-(4-hydroxy-3-methoxy-phenyl)-ethyl]-4,5-dihydro-pyrazol-1-yl]-benzoic acid) is a recently developed curcumin derivative which exhibits potent inhibitory activities against the proliferation of several tumor cell lines. In the present study, we identified Ca2+/calmodulin (Ca2+/CaM) as a direct target protein of HBC using phage display biopanning. Ca2+/CaM-expressing phages specifically bound to the immobilized HBC, and the binding was Ca2+ dependent. Moreover, flexible docking modeling demonstrated that HBC is compatible with the binding cavity for a known inhibitor, W7, in the C-terminal hydrophobic pocket of Ca2+/CaM. In biological systems, HBC induced prolonged phosphorylation of ERK1/2 and activated p21(WAF1) expression, resulting in the induction of G0/G1 cell cycle arrest in HCT15 colon cancer cells. These results suggest that HBC inhibits the cell cycle progression of colon cancer cells via antagonizing of Ca2+/CaM functions.

Study Type : In Vitro Study

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Sayer Ji
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