Ca2+ and Ca2+ channel antagonists in the control of human small cell lung carcinoma cell proliferation.
Small cell lung carcinoma cells possess voltage-dependent calcium channels (VDCCs) of the L, omega-conotoxin-sensitive and P-like type. We hypothesized that these VDCCs might regulate the secretion of autocrine growth factors and thus influence the proliferation of these cells. We found that extracellular Ca2+ plays a stimulatory role in the proliferation of the GLC8 cell line. L-type calcium channel blockers of the dihydropyridine, phenylalkylamine and benzothiazepine classes inhibited [3H]thymidine incorporation in these cells, however at concentrations higher than those required to block L-type channel function. Moreover, the growth of murine Swiss 3T3 fibroblasts which do not possess L-type Ca2+ channels, was inhibited by the Ca2+ channel antagonists at the same effective concentrations as in small cell lung carcinoma cells. omega-conotoxin and omega-agatoxin IVA, which block the N- and P-type channel respectively, had no effect on GLC8 cell proliferation. It is concluded that the presence of extracellular Ca2+ is a positive stimulus for small cell lung carcinoma cell growth. However, under our experimental conditions, the calcium channel blockers inhibited DNA synthesis most probably by a mechanism other than VDCC antagonism.
Cattaneo
M G
MG
Department of Pharmacology, University of Milano, Italy.
Gullo
M
M
Vicentini
L M
LM
D000818:Animals; D002118:Calcium / Q000494:pharmacology*; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D002147:Calmodulin / Q000037:antagonists & inhibitors; D018288:Carcinoma, Small Cell / Q000473:pathology*; D002455:Cell Division / Q000187:drug effects; D004273:DNA, Neoplasm / Q000096:biosynthesis; D005110:Extracellular Space / Q000187:drug effects / Q000378:metabolism; D005347:Fibroblasts / Q000187:drug effects; D016257:Fura-2; D006801:Humans; D008175:Lung Neoplasms / Q000473:pathology*; D051379:Mice; D009553:Nimodipine / Q000494:pharmacology; D010455:Peptides / Q000494:pharmacology; D013111:Spider Venoms / Q000494:pharmacology; D014407:Tumor Cells, Cultured; D020867:omega-Agatoxin IVA; D020866:omega-Conotoxin GVIA
D002121:Calcium Channel Blockers; D002147:Calmodulin; D004273:DNA, Neoplasm; D010455:Peptides; D013111:Spider Venoms; D020867:omega-Agatoxin IVA; D009553:Nimodipine; D020866:omega-Conotoxin GVIA; D002118:Calcium; D016257:Fura-2