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Genistein inhibits both estrogen and growth factor-stimulated proliferation of human breast cancer cells.
Cell Growth Differ. 1996 Oct; 7(10):1345-51.CG

Abstract

Genistein is a naturally occurring dietary protein tyrosine kinase (PTK) inhibitor that is hypothesized to be responsible for the lower rate of breast cancer observed in Asian women consuming soy. Although genistein is a potent in vitro PTK inhibitor, its mechanism of action in vivo is not known. In vivo, breast cancer growth is regulated by estrogens and peptide growth factors, such as epidermal growth factor (EGF), the receptor of which has intrinsic PTK activity. Therefore, genistein may block mammary epithelial cell growth by interfering with signal transduction events stimulated by estradiol or growth factors. The effect of genistein, related isoflavones, and other tyrosine kinase inhibitors on fetal bovine serum-, estradiol-, and EGF-stimulated cell growth and signal transduction pathways was examined in five human breast cancer cell lines. Genistein inhibited the growth of these cells by each of the growth stimuli with IC50 values ranging from 2.6 to over 20 micrograms/ml. Growth inhibition by genistein was cytostatic and reversible at IC50 concentrations. Related isoflavones were less potent growth inhibitors than genistein, whereas the synthetic PTK inhibitor tyrphostin A25 was an equally potent growth inhibitor. The mechanism of genistein growth inhibition in human breast cancer cells did not depend on the presence of functional estrogen receptor signaling pathways or on inhibition of EGF-receptor PTK activity. Furthermore, genistein (< or = 20 micrograms/ml) did not decrease constitutive or EGF-induced tyrosine phosphorylation as determined by Western blotting with antiphosphotyrosine antibodies. These data suggest that although genistein inhibits the growth of breast cancer cells in culture, it does so without gross inhibition of PTK activity.

Authors+Show Affiliations

Department of Pharmacology and Toxicology, University of Alabama at Birmingham 35294, USA.No affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, P.H.S.

Language

eng

PubMed ID

8891338

Citation

Peterson, G, and S Barnes. "Genistein Inhibits Both Estrogen and Growth Factor-stimulated Proliferation of Human Breast Cancer Cells." Cell Growth & Differentiation : the Molecular Biology Journal of the American Association for Cancer Research, vol. 7, no. 10, 1996, pp. 1345-51.
Peterson G, Barnes S. Genistein inhibits both estrogen and growth factor-stimulated proliferation of human breast cancer cells. Cell Growth Differ. 1996;7(10):1345-51.
Peterson, G., & Barnes, S. (1996). Genistein inhibits both estrogen and growth factor-stimulated proliferation of human breast cancer cells. Cell Growth & Differentiation : the Molecular Biology Journal of the American Association for Cancer Research, 7(10), 1345-51.
Peterson G, Barnes S. Genistein Inhibits Both Estrogen and Growth Factor-stimulated Proliferation of Human Breast Cancer Cells. Cell Growth Differ. 1996;7(10):1345-51. PubMed PMID: 8891338.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Genistein inhibits both estrogen and growth factor-stimulated proliferation of human breast cancer cells. AU - Peterson,G, AU - Barnes,S, PY - 1996/10/1/pubmed PY - 1996/10/1/medline PY - 1996/10/1/entrez SP - 1345 EP - 51 JF - Cell growth & differentiation : the molecular biology journal of the American Association for Cancer Research JO - Cell Growth Differ VL - 7 IS - 10 N2 - Genistein is a naturally occurring dietary protein tyrosine kinase (PTK) inhibitor that is hypothesized to be responsible for the lower rate of breast cancer observed in Asian women consuming soy. Although genistein is a potent in vitro PTK inhibitor, its mechanism of action in vivo is not known. In vivo, breast cancer growth is regulated by estrogens and peptide growth factors, such as epidermal growth factor (EGF), the receptor of which has intrinsic PTK activity. Therefore, genistein may block mammary epithelial cell growth by interfering with signal transduction events stimulated by estradiol or growth factors. The effect of genistein, related isoflavones, and other tyrosine kinase inhibitors on fetal bovine serum-, estradiol-, and EGF-stimulated cell growth and signal transduction pathways was examined in five human breast cancer cell lines. Genistein inhibited the growth of these cells by each of the growth stimuli with IC50 values ranging from 2.6 to over 20 micrograms/ml. Growth inhibition by genistein was cytostatic and reversible at IC50 concentrations. Related isoflavones were less potent growth inhibitors than genistein, whereas the synthetic PTK inhibitor tyrphostin A25 was an equally potent growth inhibitor. The mechanism of genistein growth inhibition in human breast cancer cells did not depend on the presence of functional estrogen receptor signaling pathways or on inhibition of EGF-receptor PTK activity. Furthermore, genistein (< or = 20 micrograms/ml) did not decrease constitutive or EGF-induced tyrosine phosphorylation as determined by Western blotting with antiphosphotyrosine antibodies. These data suggest that although genistein inhibits the growth of breast cancer cells in culture, it does so without gross inhibition of PTK activity. SN - 1044-9523 UR - https://www.unboundmedicine.com/medline/citation/8891338/Genistein_inhibits_both_estrogen_and_growth_factor_stimulated_proliferation_of_human_breast_cancer_cells_ L2 - http://cgd.aacrjournals.org/cgi/pmidlookup?view=long&amp;pmid=8891338 DB - PRIME DP - Unbound Medicine ER -