GENISTEIN AS AN INDUCER OF TUMOR-CELL DIFFERENTIATION - POSSIBLE MECHANISMS OF ACTION

Decreased activity of either topoisomerases or tyrosine kinases has be en implicated in the differentiation of a number of cell types. It is therefore conceivable that genistein, because of its reported ability to inhibit these activities in vitro, may be an Inducer of cellular di fferentiation. We investigated this possibility in human promyelocytic HL-60 and erythroid K-562 leukemia cells and in human SK-MEL-131 mela noma cells, Our results indicated that genistein, in a dose-dependent manner, inhibited cell multiplcation and induced cell differentiation. The maturing HL-60 cells acquired granulocytic and monocytic markers. The differentiating K-562 cells stained positively with benzidine, wh ich indicates the production of hemoglobin, an erythroid marker. Follo wing genistein treatment, maturing SK-MEL-131 melanoma cells formed de ndrite-like structures and exhibited increased tyrosinase activity and melanin content, Experiments were designed to identify the molecular mechanism of genistein's action. Data from our laboratory suggest that this isoflavone triggers the pathway that reads to cellular different iation by stabilizing protein-linked DNA strand breakage. Other possib le mechanisms reported in the literature are discussed.