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Effects of calcium channel blockers on cellular apoptosis: implications for carcinogenic potential
1Cardiovascular and Pulmonary Research Institute, Department of Biochemistry, MCP Hahnemann University School of Medicine, Pittsburgh, Pennsylvania, USA.
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.
Insights
Calcium channel blockers (CCBs) do not increase cancer risk. Research shows CCBs do not promote tumor growth and may even inhibit it, with no evidence supporting a link to cancer development.
Area of Science:
- Pharmacology
- Oncology
- Cell Biology
Background:
- Retrospective studies suggested calcium channel blockers (CCBs) may increase cancer risk by interfering with apoptosis.
- The proposed mechanism involved CCBs inhibiting apoptosis, a crucial cell death process, potentially leading to tumor promotion.
Purpose of the Study:
- To critically review the scientific literature on the effects of CCBs on apoptosis and tumor development.
- To evaluate the proposed biologic mechanism linking CCBs, apoptosis, and cancer.
Main Methods:
- Comprehensive literature review of experimental models and epidemiologic studies.
- Focused on the impact of pharmacologic CCBs on apoptosis and neoplastic growth.
Main Results:
- CCBs exhibit complex and contradictory effects on cellular apoptosis.
- CCBs did not promote neoplastic growth in experimental cancer models; some models showed inhibited tumor growth.
- Large epidemiologic studies failed to support an increased cancer risk associated with CCB use.
Conclusions:
- The scientific literature does not support a biologic link between CCB use and increased human cancer risk via modulation of apoptosis.
- The proposed mechanism of CCBs inhibiting apoptosis to promote cancer is not substantiated by current evidence.