Growth inhibition and induction of specific hepatic phenotype expression by retinoic acid in HEPG2 cells

Retinoic acid, the active metabolite of vitamin A, plays a role in the grow th and differentiation of a variety of normal and malignant cells. In respo nse to 5 mu M retinoic acid the human hepatoma-derived cell line HepG2 unde rwent significant growth inhibition (not associated with cell death), which reached a level of 80% in comparison with controls, after 12 days of conti nuous treatment. Retinoic acid also induced morphological changes in these cells, in particular the development of canalicular-like structures, indica ting progression to a more differentiated phenotype. In addition, a reduced expression alpha-fetoprotein was found. We suggest that our results may be important for the design of novel therapeutic approaches using RA for the treatment of liver tumors.