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Cholera Toxin Triggers Apoptosis in Human Lung Cancer Cell Lines¹

Louis-Charles Simard Research Center, Montreal Cancer Institute [M. A., R. B., G. Z-S., J. P., J. V.], and Division of Hematology-Oncology Department of Medicine, Notre-Dame Pavilion, Centre Hospitalier de l'Universitè de Montreal and University of Montreal, 1560 Sherbrooke Street East, Montreal, Quebec H2L 4M1 Canada

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.

¹ J.V. was a scholar of the Medical Research Council of Canada and the work reported here was supported by funds from the Center de Recherche Louis-Charles Simard and the Fonds de Recherche en Santé du Québec to J.V. and by funds from the Medical Research Council of Canada (to R. B.). R. B. is a scholar of the Medical Research Council of Canada and the Cancer Research Society.

² To whom requests for reprints should be addressed. Phone: (514) 281 6000, ext. 6615; Fax: (514) 896 4689; E-mail: bertranr@ere.umontreal.ca.

³ Present address: Sanofi Research Division, Malvern, PA 19355.

Received 3/18/97. Accepted 5/14/97.