title: Daidzein-estrogen interaction in the rat uterus and its effect on human breast cancer cell growth.
abstract: Sex hormone replacement therapy provides several advantages in the quality of life for climacteric women. However, estrogen-induced cell proliferation in the uterus and mammary gland increases the risk of cancer development in these organs. The lower incidence of mammary cancer in Asian women as compared with Western women has been attributed to high intake of soy isoflavones, including genistein. We have previously shown that genistein induces an estradiol-like hypertrophy of uterine cells, but does not induce cell proliferation, uterine eosinophilia, or endometrial edema. It also inhibits estradiol-induced mitosis in uterine cells and hormone-induced uterine eosinophilia and endometrial edema. Nevertheless, genistein stimulates growth of human breast cancer cells in culture; therefore, it is not an ideal estrogen for use in hormone replacement therapy (HRD). The present study investigated the effect of another soy isoflavone, daidzein (subcutaneous, 0.066 mg/kg body weight), in the same animal model, and its effect on responses induced by subsequent treatment (1 h later) with estradiol-17β (E(2); subcutaneous, 0.33 mg/kg body weight). In addition, we investigated the effects of daidzein (1 μg/mL) or E(2) on the growth of human breast cancer cells in culture. Results indicate that daidzein stimulates growth of breast cancer cells and potentiates estrogen-induced cell proliferation in the uterus. We suggest caution for the use of daidzein or formulas containing this compound in HRD. Future research strategies should be addressed in the search for new phytoestrogens that selectively inhibit cell proliferation in the uterus and breast.
authors.affiliation: Institute of Biomedical Sciences (ICBM), School of Medicine, University of Chile, Santiago, Chile.
authors.forename: Leonardo
authors.initials: L
authors.lastname: Gaete
authors.forename: Andrei N
authors.initials: AN
authors.lastname: Tchernitchin
authors.forename: Rodrigo
authors.initials: R
authors.lastname: Bustamante
authors.forename: Joan
authors.initials: J
authors.lastname: Villena
authors.forename: Igor
authors.initials: I
authors.lastname: Lemus
authors.forename: Manuel
authors.initials: M
authors.lastname: Gidekel
authors.forename: Gustavo
authors.initials: G
authors.lastname: Cabrera
authors.forename: Paola
authors.initials: P
authors.lastname: Astorga
mesh_terms: D000818:Animals; D018931:Antineoplastic Agents, Hormonal / Q000494:pharmacology; D001943:Breast Neoplasms / Q000473:pathology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004347:Drug Interactions; D004958:Estradiol / Q000494:pharmacology; D004967:Estrogens / Q000494:pharmacology*; D005260:Female; D006801:Humans; D007529:Isoflavones / Q000494:pharmacology*; D061986:MCF-7 Cells; D048789:Phytoestrogens / Q000494:pharmacology; D010936:Plant Extracts / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013025:Glycine max / Q000737:chemistry; D014599:Uterus / Q000187:drug effects* / Q000378:metabolism
chemical_list: D018931:Antineoplastic Agents, Hormonal; D004967:Estrogens; D007529:Isoflavones; D048789:Phytoestrogens; D010936:Plant Extracts; D004958:Estradiol; C004742:daidzein