Cholera toxin triggers apoptosis in human lung cancer cell lines.
Cholera toxin (ChT) inhibits signals generated by multiple growth factors in human lung cancer cells, resulting in cell growth inhibition. We now report that ChT triggers apoptosis as shown by DNA fragmentation and activation of caspases cleaving poly(ADP-ribose) polymerase and lamin B. Apoptosis induced by ChT in a small cell lung cancer cell line is not affected by manipulations of intracellular cAMP through preincubation with isobutylmethylxanthine but can be modestly increased through inhibition of protein kinase C with chelerythrine. Thus, apoptosis is actively suppressed in lung cancer cells by a ChT-sensitive-growth regulatory pathway, and these observations may have significant implications in the development of novel strategies for lung cancer treatment.
Allam
M
M
Louis-Charles Simard Research Center, Montreal Cancer Institute, Department of Medicine, Centre Hospitalier de l'Universitè de Montrealand University of Montreal, Quebec, Canada.
Bertrand
R
R
Zhang-Sun
G
G
Pappas
J
J
Viallet
J
J
D015056:1-Methyl-3-isobutylxanthine / Q000494:pharmacology; D000470:Alkaloids; D017209:Apoptosis; D053119:Benzophenanthridines; D002289:Carcinoma, Non-Small-Cell Lung / Q000473:pathology*; D018288:Carcinoma, Small Cell / Q000473:pathology*; D002772:Cholera Toxin / Q000494:pharmacology*; D000242:Cyclic AMP / Q000502:physiology; D053938:DNA Fragmentation / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006801:Humans; D008175:Lung Neoplasms / Q000473:pathology*; D010617:Phenanthridines / Q000494:pharmacology; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D014407:Tumor Cells, Cultured; D051028:bcl-2-Associated X Protein
D000470:Alkaloids; D053119:Benzophenanthridines; D004791:Enzyme Inhibitors; D010617:Phenanthridines; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D051028:bcl-2-Associated X Protein; D002772:Cholera Toxin; D000242:Cyclic AMP; C016299:chelerythrine; D015056:1-Methyl-3-isobutylxanthine