Retinoids and alcohol-related carcinogenesis

Abstract

Chronic and excessive alcohol intake is associated with an increased incidence of a variety of cancers (e.g., liver, oral cavity, esophagus, colorectal and breast). Long-term alcohol intake results in impaired nutritional status of retinoic acid (RA), the most active derivative of vitamin A, which may provide a promoting environment for tumor formation. Recent studies demonstrate that chronic alcohol-induced hepatocellular proliferation, which may convert hepatocytes from a state of resistance to a carcinogen to a state of high susceptibility, is due to alcohol-impaired RA metabolism and signaling and crosstalk with the Jun N-terminal kinases-dependent signaling pathway. Further, the restoration of hepatic RA homeostasis by treatment with either RA supplementation or inhibitors of RA catabolism can suppress alcohol-induced hepatocyte hyperproliferation and restore alcohol-deregulated apoptosis, thereby reducing the risk of alcohol-promoted hepatocellular carcinogenesis. These studies indicate the importance of RA actions in the prevention and/or treatment of alcohol-related carcinogenic process in the liver and other organs.