In vitro growth inhibition of human colonic tumor cells by Verapamil

doi:10.3748/wjg.v11.i15.2255

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World Journal of Gastroenterology

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1007-9327

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Baishideng Publishing Group Inc, 7041 Koll Center Parkway, Suite 160, Pleasanton, CA 94566, USA

Colorectal Cancer

World J Gastroenterol. Apr 21, 2005; 11(15): 2255-2259
Published online Apr 21, 2005. doi: 10.3748/wjg.v11.i15.2255

In vitro growth inhibition of human colonic tumor cells by Verapamil

Qi-Zhen Cao, Gang Niu, Huan-Ran Tan

Qi-Zhen Cao, Huan-Ran Tan, Department of Pharmacology, Peking University Health Science Center, Peking University, Beijing 100083, China

Gang Niu, Beijing N&N Genetech Company, Beijing 100088, China

Author contributions: All authors contributed equally to the work.

Supported by the Foundation of the National New Drug Research of China, No. 96-901-05-197

Correspondence to: Huan-Ran Tan, Department of Pharmacology, Peking University Health Science Center, Peking University, Beijing 100083, China. tanlab@sun.bjmu.edu.cn

Telephone: +86-10-8280-2004 Fax: +86-10-8280-2004

Received: March 30, 2004
Revised: March 31, 2004
Accepted: May 24, 2004
Published online: April 21, 2005

Abstract

AIM: To investigate the effects and mechanisms of Verapamil on cultured human colonic tumor (HCT) cells.

METHODS: HCT cells were treated with different concentrations of Verapamil, and their proliferation was examined by MTT assay. The areas of sub-diploid peak were measured by flow cytometry, and the DNA ladder was found by agarose gel electrophoresis. The characteristic changes in morphology were observed under light microscopy. The cell nuclei (propidium iodide labeled, PI-labeled) and cellular distribution and concentration of calcium (Fluo-3-labeled) were studied by using laser confocal scanning microscope.

RESULTS: The proliferation of HCT cells was inhibited by different concentrations of Verapamil. With the increase in concentration of Verapamil, the percent of G0-G1 phase cells in HCT cells increased and that of S phase cells decreased. After treating with different concentrations of Verapamil, flow cytometry showed that HCT cells were enlarged in areas of sub-diploid in a dose-dependent manner. Gel electrophoresis results displayed a typical DNA ladder. On staining with Wrights-Giemsa, the typical cellular apoptosis morphologic changes were also observed. PI-labeled cell nuclei were found markedly changed. In addition, we inspected that the 100 μmol/L Verapamil could increase the intracellular calcium ion concentration [Ca²⁺]_i in HCT cells.

CONCLUSION: Verapamil can inhibit proliferation of HCT cells via inducing cell apoptosis.

Keywords: HCT, Verapamil