Genistein as an inducer of tumor cell differentiation : possible mechanisms of action.

Journal Article · Sun Jan 01 04:00:00 EST 1995 · Proc. Soc. Exp. Biol. Med.

DOI:https://doi.org/10.3181/00379727-208-43841· OSTI ID:937709

Constantinou, A; Huberman, E

Decreased activity of either topoisomerases or tyrosine kinases has been 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 differentiation. We investigated this possibility in human promyelocytic HL-60 and erythroid K-562 leukemia cells and in human SK-MEL-131 melanoma cells. Our results indicated that genistein, in a dose-dependent manner, inhibited cell multiplication and induced cell differentiation. The maturing HL-60 cells acquired granulocytic and monocytic markers. The differentiating K-562 cells stained positively with benzidine, which indicates the production of hemoglobin, an erythroid marker. Following genistein treatment, maturing SK-MEL-131 melanoma cells formed dendrite-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 leads to cellular differentiation by stabilizing protein-linked DNA strand breakage. Other possible mechanisms reported in the literature are discussed.

• Research Organization: Argonne National Laboratory (ANL)
• Sponsoring Organization: ER
• DOE Contract Number: AC02-06CH11357
• OSTI ID: 937709
• Report Number(s): ANL/CMB/JA-13873
• Journal Information: Proc. Soc. Exp. Biol. Med., Journal Name: Proc. Soc. Exp. Biol. Med. Journal Issue: 1 ; Jan. 1995 Vol. 208; ISSN PSEBAA; ISSN 0037-9727
• Country of Publication: United States
• Language: ENGLISH

Related Subjects

59 BASIC BIOLOGICAL SCIENCES
BENZIDINE
CELL DIFFERENTIATION
DNA
HEMOGLOBIN
IN VITRO
LEUKEMIA
MELANIN
MELANOMAS
PHOSPHOTRANSFERASES
PRODUCTION
TUMOR CELLS
TYROSINASE
TYROSINE