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Stimulatory effect of genistein and apigenin on the growth of breast cancer cells correlates with their ability to activate ER alpha

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Summary

Genistein and apigenin are phytoestrogens present in commercial preparations used for the treatment of postmenopausal symptoms. In this study, we assessed the influence of these compounds on mammary tumor growth. Both compounds stimulate the proliferation of MCF-7 and T47D cells [estrogen receptor alpha (ERα-positive)], but do not stimulate the proliferation of an ERα-negative cell line (MDA-MB-435 cells). Genistein appeared more efficient in this regard due to its higher binding affinity for ERα, a property explained by a structural analysis of the binding of these compounds to the ERα’s ligand binding domain. As previously described for estradiol (E2), genistein and apigenin down regulated ERα and enhanced estrogen response element (ERE)-dependent gene expression. The additional finding that genistein antagonizes the anti-proliferative effect of hydroxytamoxifen suggests phytoestrogens may be detrimental in women with breast cancer who are being treated with tamoxifen. In addition, because of their ability to stimulate breast cell growth, the widespread use of phytoestrogens in postmenopausal women could be detrimental.

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Acknowledgements

We are grateful to Dr D. Larsimont (Service d’Anatomie Pathologique, Institut Jules Bordet, Brussels, Belgium) for the interpretation of immunocytochemical data. We are thankful to Dr Heidi Weiss (Breast Center, Baylor College of Medicine) for the statistical analysis and to Shirley Pennington for her assistance in preparing the manuscript. This work was supported by R01 CA78480, R01 CA101211 (PHB, Baylor College of Medicine), a DOD fellowship (DGD, Baylor College of Medicine), and the MEDIC Foundation (Institut Jules Bordet).

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Authors and Affiliations

  1. Departments of Medicine and Molecular and Cellular Biology, Breast Center, Baylor College of Medicine, Houston, TX, USA

    Hye-Sook Seo, David G. DeNardo & Powel H. Brown

  2. Synthèse, Structure et Fonction de Molécules Bioactives, Université Pierre et Marie Curie-Paris6, UMR 7613, Paris, France

    Yves Jacquot

  3. Laboratoire J.-C. Heuson de Cancérologie Mammaire, Service de Médicine Interne, Institut Jules Bordet, Université Libre de Bruxelles, Brussels, Belgium

    Ioanna Laïos, Doris Salazar Vidal, Carmen Rojas Zambrana & Guy Leclercq

  4. Departments of Medicine and Molecular and Cellular Biology, Breast Center, Baylor College of Medicine, One Baylor Plaza, Houston, TX, 77030, USA

    Powel H. Brown

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  1. Hye-Sook Seo
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Seo, HS., DeNardo, D.G., Jacquot, Y. et al. Stimulatory effect of genistein and apigenin on the growth of breast cancer cells correlates with their ability to activate ER alpha. Breast Cancer Res Treat 99, 121–134 (2006). https://doi.org/10.1007/s10549-006-9191-2

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