Effects of calcium channel blockers on cellular apoptosis: implications for carcinogenic potential.
BACKGROUND: A small number of well-publicized, retrospective epidemiologic reports have suggested a causal relation between the use of calcium channel blockers (CCBs) for the treatment of hypertension and an increased risk for cancer. The biologic mechanism proposed to explain this possible relation is that CCBs interfere with apoptosis, an active cell death process required for the regulation of normal cell populations in the body. Because an elevation in cellular calcium (Ca2+) is thought to be involved in apoptosis, it has been argued that CCBs could inhibit apoptosis, leading directly to tumor promotion. METHODS: A comprehensive and critical review of the scientific literature was conducted specifically to evaluate the effects of pharmacologic CCBs on apoptosis and tumor development in various experimental models. RESULTS: A review of the scientific literature revealed that CCBs have complex and often contradictory effects on cellular apoptosis. In various experimental models of cancer, CCBs did not promote neoplastic growth. By contrast, CCB treatment was associated with an inhibition of tumor growth in certain models of neoplasia and was also an effective adjuvant therapy in the treatment of certain drug-resistant tumors. Additional large epidemiologic studies have failed to support the hypothesis that CCB use is associated with an increased susceptibility for cancer. CONCLUSIONS: A biologic link between the use of CCBs and increased human risk for cancer development as a result of modulating cellular apoptosis is not supported by the scientific literature.