title: Genistein in the control of breast cancer cell growth: insights into the mechanism of action in vitro.
abstract: Genistein significantly inhibited cell growth (IC50 around 10 microM) of MCF-7, MDAMB-231 and HBL-100 cell lines, but not of skin-derived fibroblasts and counteracted the growth-stimulatory effects exerted by estradiol and growth factors. It abolished the paracrine stimulation observed in MCF-7 cells in co-culture with MDAMB-231 or fibroblasts. Genistein-treated cells accumulated in the S and G2/M phases of the cell cycle and underwent apoptosis. Genistein decreased tyrosine phosphorylation induced upon treatment with transforming growth factor-alpha. Finally, genistein bound the estrogen receptor (ER) (relative affinity constant Kd = 4 nM), induced pS2 and cathepsin-D transcription and increased nuclear ER levels.
authors.affiliation: Istituto Nazionale per lo Studio e la Cura dei Tumori, Milan, Italy.
authors.forename: L
authors.initials: L
authors.lastname: Fioravanti
authors.forename: V
authors.initials: V
authors.lastname: Cappelletti
authors.forename: P
authors.initials: P
authors.lastname: Miodini
authors.forename: E
authors.initials: E
authors.lastname: Ronchi
authors.forename: M
authors.initials: M
authors.lastname: Brivio
authors.forename: G
authors.initials: G
authors.lastname: Di Fronzo
mesh_terms: D000970:Antineoplastic Agents / Q000378:metabolism / Q000494:pharmacology*; D017209:Apoptosis; D001667:Binding, Competitive; D001943:Breast Neoplasms / Q000378:metabolism / Q000473:pathology; D002453:Cell Cycle / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D004958:Estradiol / Q000378:metabolism / Q000494:pharmacology; D005260:Female; D005347:Fibroblasts / Q000166:cytology / Q000187:drug effects; D019833:Genistein / Q000378:metabolism / Q000494:pharmacology*; D006133:Growth Substances / Q000494:pharmacology; D006801:Humans; D010766:Phosphorylation; D011960:Receptors, Estrogen / Q000378:metabolism; D014407:Tumor Cells, Cultured / Q000187:drug effects
chemical_list: D000970:Antineoplastic Agents; D006133:Growth Substances; D011960:Receptors, Estrogen; D004958:Estradiol; D019833:Genistein