In vitro growth inhibition of human colonic tumor cells by Verapamil.
OBJECTIVE
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 micromol/L Verapamil could increase the intracellular calcium ion concentration [Ca(2+)](i) in HCT cells.


CONCLUSIONS
Verapamil can inhibit proliferation of HCT cells via inducing cell apoptosis.
Cao
Qi-Zhen
QZ
Department of Pharmacology, Peking University Health Science Center, Peking University, Beijing 100083, China.
Niu
Gang
G
Tan
Huan-Ran
HR
D017209:Apoptosis / Q000187:drug effects*; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D002455:Cell Division / Q000187:drug effects; D045744:Cell Line, Tumor; D003110:Colonic Neoplasms / Q000188:drug therapy* / Q000473:pathology*; D005434:Flow Cytometry; D006801:Humans; D066298:In Vitro Techniques; D014700:Verapamil / Q000494:pharmacology*
D002121:Calcium Channel Blockers; D014700:Verapamil