Cellular Differentiation: Importance in Hepatocarcinogenesis and Modulator Role of ß-Carotene

Abstract

This review focuses the relationship between oval cell differentiation and the cellular origin of hepatic cancer, as well as the recent studies on the action of ß-carotene in cellular differentiation. Oval cells proliferate in the liver during the early stages of hepatocarcinogenesis, with the capability to differentiate to both hepatocytes and biliary duct cells, as demonstrated by in vivo models of hepatic cellular differentiation. Hepatic cancer can be derived from oval cells after the exposure to hepatocarcinogens, by an irreversible block in the process of normal differentiation, and generation of immortal transformed cells with proliferative potential. It has been demonstrated, in in vitro models, that ß-carotene (and other carotenoids without provitamin A activity) induces cellular differentiation. Moreover, it has been observed in in vivo models of hepatocarcinogenesis and of cellular differentiation, that the carotenoid reduces the number of oval cells at the end of the experimental period. These findings indicate that ß-carotene can promote complete terminal differentiation of oval cells and suggest that these effect may have implications for chemoprevention of hepatic cancer.