The effect of H2 antagonists on proliferation and apoptosis in human colorectal cancer cell lines
Abstract
Cimetidine is known to enhance the survival of gastro-intestinal cancer patients, though the mechanisms involved are incompletely understood. Postulated modes of action include blocking the proliferative effect of tumors and inhibiting T suppressor cell activity, both of which are thought to be mediated by histamine type 2 receptors. Apoptotic cell death may offer an alternative explanation for reduced cell growth. We aimed to examine the effects of histamine, cimetidine, and ranitidine on in vitro proliferation and apoptosis in two human colorectal cancer cell lines, Caco-2 and LoVo. A cell proliferation assay was used as an index of cell growth. Histamine receptor status was determined by quantifying cyclic adenosine monophosphate and apoptosis via DNA fragmentation. Results show that histamine (10(-5) to 10(-9) M) had no effect on the growth of either cell line. The proliferation of Caco-2 was inhibited by ranitidine (10(-7) M) alone and in combination with histamine. Cimetidine (10(-5) M) only suppressed the growth of Caco-2 in the presence of histamine. The H2 antagonists had no effect on LoVo irrespective of histamine. There was no accumulation of cyclic adenosine monophosphate in Caco-2 cells in response to histamine at a similar concentration. Apoptosis was induced in Caco-2 by both antisecretory drugs, and only ranitidine caused apoptotic cell death in LoVo cells. We conclude that cimetidine and ranitidine inhibit Caco-2 cancer cells in vitro, independently of the…
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