CALCIUM-CHANNEL BLOCKERS AND THE RISK OF CANCER - A PRECLINICAL ASSESSMENT

The preclinical evidence for a potential influence of calcium channel blockers (CCBs) on carcinogenesis is discussed in the light of a broad database from rodent carcinogenicity studies as well as literature da ta. In all bioassays performed in rats and mice on the dihydropyridine CCBs - nifedipine, nimodipine, nisoldipine, and nitrendipine - no evi dence was found for a carcinogenic potential of these compounds. Calci um is an essential intracellular signal for cell proliferation and apo ptosis. The crucial role of increased cell proliferation in all stages of carcinogenesis is well documented. Some indirect experimental evid ence also points to a role of defective apoptosis in tumor promotion. CCBs uniformly inhibit cell proliferation, whereas the influence of CC Bs on apoptosis is inconsistent, resulting in an inhibition or increas e in apoptosis dependent on cell type. Accordingly, antitumorigenic ef fects of CCBs have been reported based on their antiproliferative acti on. A tumor-promoting effect of CCBs based on inhibition of apoptosis, however, remains purely speculative and, in fact, can be denied based on the results of in vivo bioassays. It is therefore concluded that t here is no preclinical evidence that should give rise to concern over the carcinogenic potential of dihydropyridine-type CCBs.