INHIBITION OF GROWTH AND INDUCTION OF DIFFERENTIATION OF METASTATIC MELANOMA-CELLS IN-VITRO BY GENISTEIN - CHEMOSENSITIVITY IS REGULATED BYCELLULAR P53

We have investigated the effect of the soybean isoflavone genistein on the growth and differentiation of human melanoma cells. Four human me lanoma cell lines, either completely lacking or containing different l evels of wild-type p53, were treated with genistein in vitro in cultur e. It has been found that genistein significantly inhibited cell growt h and that the chemosensitivity might depend on cellular p53 content. Specifically, the data suggest that high levels of wild-type p53 expre ssion make cells resistant to genistein's growth-inhibitory action. Fu rther support for this observation came from the stable transfection s tudies in which p53 transfectants expressing high levels of wild-type p53 became resistant to genistein. With respect to cell differentiatio n, our study showed that genistein increased melanin content and tyros inase activity and caused the cells to form dendrite-like structures. cells lacking p53 responded more than cells with p53 to dendrite-like structure formation. We also observed that genistein-induced different iation involved an increase in tyrosinase mRNA level; the mechanisms b y which genistein increases tyrosinase transcripts remain to be elucid ated. Genistein treatment of the melanoma cell fines resulted in cell cycle arrest at G(2)/M check point and no significant apoptosis was ob served.