Verapamil inhibits L-type calcium channel mediated apoptosis in human colon cancer cells.
OBJECTIVE
Treatment with calcium channel blockers have been associated with increased colon cancer mortality in epidemiologic studies. We examined the potential expression and function of calcium channels in two human colon cancer cell lines.


METHODS
Both primary (collected at operation) and commercially-available human colon cancer cell lines were used. The colon cancer cells were incubated with a calcium channel blocker (verapamil) and a calcium channel agonist (BayK 8644) at clinically relevant concentrations. L-type calcium channel mRNA was determined by reverse-transcription polymerase chain reaction. Intracellular calcium ion levels were measured with fluorometry and apoptosis with flow cytometry.


RESULTS
Both types of cells expressed L-type calcium channel mRNA, comprising an alpha-1D and a beta-3 subunit, whereas the cells were negative for N-type and P-type channels. The selective calcium channel agonist (BayK 8644), dose-dependently increased intracellular calcium ion levels and the level of apoptosis in primary human colon cancer cells. Pretreatment with verapamil completely abolished both calcium channel agonist-induced influx of calcium and apoptosis in these cells.


CONCLUSIONS
These data demonstrate that human colon cancer cells express L-type calcium channels that mediate calcium influx and apoptosis, which warrants further studies to determine whether calcium channel blockers may promote colon cancer growth.
Zawadzki
Antoni
A
Department of Surgery, Malmö University Hospital, Lund University, Malmö, Sweden.
Liu
Qing
Q
Wang
Yusheng
Y
Melander
Arne
A
Jeppsson
Bengt
B
Thorlacius
Henrik
H
D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects*; D002120:Calcium Channel Agonists / Q000494:pharmacology; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D020746:Calcium Channels, L-Type / Q000187:drug effects* / Q000378:metabolism; D018929:Cell Culture Techniques; D045744:Cell Line, Tumor; D003110:Colonic Neoplasms / Q000378:metabolism / Q000473:pathology*; D006801:Humans; D012333:RNA, Messenger / Q000378:metabolism; D014700:Verapamil / Q000494:pharmacology*
D002120:Calcium Channel Agonists; D002121:Calcium Channel Blockers; D020746:Calcium Channels, L-Type; D012333:RNA, Messenger; D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester; D014700:Verapamil