Selenium, calcium channel blockers, and cancer risk--the Yin and Yang of apoptosis?
It is increasingly clear that apoptosis plays a crucial role in the promotional phase of cancer development. Initiated pre-neoplastic clones in rat liver experience a high rate of apoptosis, and this rate has an important impact on the survival and growth of these clones. Suppression of apoptosis appears to be a universal property of cancer promoters, suggesting conversely that agents which inhibit cancer induction during the promotional phase increase the rate of apoptosis in initiated cells. Modulation of apoptosis is a likely explanation for recent striking evidence that use of calcium channel blockers substantially increases, whereas supplemental selenium substantially decreases, human cancer incidence. Non-genotoxic measures which are likely to upregulate apoptosis in pre-neoplastic/neoplastic cells--and thus may be useful in prevention and/or therapy--include selenium, retinoids/carotenoids, green tea polyphenols, caloric restriction, downregulation of IGF-I activity, high-dose tamoxifen and other protein kinase C antagonists, withdrawal or blockade of trophic hormones, isoflavones, limonene, vitamin D and cholecalciferol analogs, dietary fiber/sodium butyrate, hyperthermia, benzaldehyde derivatives, and creatine.
Nutrition 21, San Diego, CA 92109, USA.
M F
MF
McCarty
D000818:Animals; D016588:Anticarcinogenic Agents / Q000627:therapeutic use*; D017209:Apoptosis / Q000187:drug effects; D002121:Calcium Channel Blockers / Q000009:adverse effects* / Q000633:toxicity; D002273:Carcinogens / Q000633:toxicity; D006801:Humans; D015994:Incidence; D008113:Liver Neoplasms / Q000139:chemically induced / Q000473:pathology; D008954:Models, Biological; D009369:Neoplasms / Q000453:epidemiology* / Q000473:pathology / Q000517:prevention & control; D011230:Precancerous Conditions / Q000139:chemically induced / Q000473:pathology; D051381:Rats; D012307:Risk Factors; D012643:Selenium / Q000627:therapeutic use*
D016588:Anticarcinogenic Agents; D002121:Calcium Channel Blockers; D002273:Carcinogens; D012643:Selenium