Journal Mobile Options
Table of Contents
Vol. 84, No. 2, 2009
Issue release date: August 2009
Pharmacology 2009;84:68–73

Genistein in the Presence of 17β-Estradiol Inhibits Proliferation of ERβ Breast Cancer Cells

Rajah T.T. · Du N. · Drews N. · Cohn R.
Department of Biological Sciences, DePaul University, Chicago, Ill., USA

Individual Users: Register with Karger Login Information

Please create your User ID & Password

Contact Information

I have read the Karger Terms and Conditions and agree.

To view the fulltext, please log in

To view the pdf, please log in


Background/Aim:Genistein, a soy component, has been shown to have a biphasic proliferative effect in breast cancer cells, inhibiting in vitro cell proliferation at high concentrations (>10 μmol/l), while stimulating cell proliferation at lower concentrations (<10 μmol/l). However, epidemiological studies have shown an inverse correlation between the intake of genistein and the incidence of breast cancer. One of the possible reasons for this discrepancy could be the differing status of the estrogen receptor (ERα and/or ERβ). Genistein selectively binds to ERβ with strong affinity and thereby could be a potential chemotherapeutic agent against breast cancer of the ERα-negative and ERβ-positive type. Therefore, the objective of the present study was to determine whether the proliferative effects of genistein were caused by its activity as a selective ERβ agonist or merely as an antiestrogen. Method: This study was carried out in MDA-MB-231 (ERβ) and T47D (ERα and ERβ) human breast cancer cells. Cell proliferation was determined by the MTT (3-[4,5-dimethyl-2-thiazolyl]-2,5-diphenyl-2H-tetrazolium bromide) assay. The cells were grown in estrogen-starved media and exposed to genistein at different concentrations for 72 h, either in the presence or absence of 17β-estradiol. Results: A significant decrease in cell proliferation was seen in MDA-MB-231 cells at low concentrations of genistein in the presence of 17β-estradiol, as compared to genistein alone. In T47D cells, which are known to have a predominance of ERα over ERβ, genistein showed a biphasic cell proliferative response both in the presence and absence of 17β-estradiol. Conclusions:Our results suggest that in cells with a predominance of ERα, genistein acts as an agonist to ERα, and in cells with ERβ alone, genistein most likely acts as an antiestrogen. Our results also suggest that genistein could be useful as a chemotherapeutic agent in premenopausal women with breast cancer of the ERα-negative and ERβ-positive type.

Copyright / Drug Dosage

Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher or, in the case of photocopying, direct payment of a specified fee to the Copyright Clearance Center.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in goverment regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.


  1. Kurzer MS: Soy consumption for reduction of menopausal symptoms. Inflammopharmacology 2008;16:227–229.
  2. Ingram D, Sander K, Kolybaba M, Lopez D: Case-control study of phyto-oestrogens and breast cancer. Lancet 1997;350:990–994.
  3. Branca F, Lorenzetti S: Health effects of phytoestrogens. Forum Nutr 2005;57:100–111.
  4. Hseih CY, Santell RC, Haslam SZ, Helferich WG: Estrogenic effects of genistein on the growth of estrogen receptor-positive human breast cancer (MCF7) cells in vitro and in vivo. Cancer Res 1998;58:3833–3838.
  5. Messina M, McCaskill-Stevens W, Lampe JW: Addressing the soy and breast cancer relationship: review, commentary and workshop proceedings. J Natl Cancer Inst 2006;98:1275–1284.
  6. Strom A, Hartman J, Foster JS, Kietz S, Wimalasena J, Gustafsson JA: Estrogen receptor β inhibits 17β-estradiol-stimulated proliferation of the breast cancer cell line T47D. Proc Natl Acad Sci 2004;101:1566–1571.
  7. Covaleda AMS, Berg H, Vervoort J, Saag P, Strom A, Gustafsson JA, Rietjens I, Murk AJ: Influence of cellular ERα/ERβ ratio on the ERα-agonist induced proliferation of human T47D breast cancer cells. Toxicol Sci 2008;105:303–311.
  8. Speirs V: The evolving role of oestrogen receptor β in clinical breast cancer. Breast Cancer Res 2008;10:111.
  9. Kuiper GG, Carlsson B, Grandien K, Enmark E, Haggblad J, Nilsson S, Gustafsson JA: Comparison of the ligand binding specificity and transcript tissue distribution of estrogen receptors alpha and beta. Endocrinology 1997;138:863–870.
  10. McCarty MF: Isoflavones made simple – genistein’s agonist activity for the beta-type estrogen receptor mediates their health benefits. Med Hypotheses 2006;66:1093–1114.
  11. Cappelletti V, Miodini P, DiFronzo G, Daidone MG: Modulation of estrogen receptor-β isoforms by phytoestrogens in breast cancer cells. Int J Oncol 2006;28:1185–1191.
  12. Tong D, Schuster E, Seifert M, Czerwenka K, Leodolter S, Zeillinger R: Expression of estrogen receptor beta isoforms in human breast cancer tissues and cell lines. Breast Cancer Res Treat 2002;71:249–255.
  13. Girault I, Andrieu C, Tozlu S, Spyratos F, Bieche I, Lidereau R: Altered pattern of alternatively spliced estrogen receptor β transcripts in breast carcinoma. Cancer Lett 2004;215:101–112.
  14. Li Z, Li J, Mo B, Hu C, Liu H, Qi H, Wang X, Xu J: Genistein induces cell apoptosis in MDA-MB-231 breast cancer cells via the mitogen activated protein kinase pathway. Toxicol In Vitro 2008;22:1749–1753.
  15. Shon YH, Park SD, Nam KS: Effective chemopreventive activity of genistein against human breast cancer cells. J Biochem Mol Biol 2006;39:448–451.
  16. Wang C, Kurzer MS: Phytoestrogen concentration determines effects on DNA synthesis in human breast cancer cells. Nutr Cancer 1997;28:236–247.
  17. Maggiolini M, Bonofiglio D, Marsico S, Panno ML, Cenni B, Picard D, Ando S: Estrogen receptor α mediates the proliferative but not the cytotoxic dose-dependent effects of two major phytoestrogens on human breast cancer cells. Mol Pharmacol 2001;60:595–602.
  18. Power KA, Thompson LU: Ligand-induced regulation of ERα and ERβ is indicative of human breast cancer cell proliferation. Breast Cancer Res Treat 2003;82:209–221.

    External Resources

  19. Sotoca AM, Ratman D, Saag PVD, Strom A, Gustafsson JA, Vervoort J, Rietjens IMCM, Murk AJ: Phytoestrogen-mediated inhibition of proliferation of the human T47D breast cancer cells depends on the ERα/ERβ ratio. J Steroid Biochem Mol Biol 2008;112:171–178.
  20. Chang EC, Frasor J, Komm B, Katzenellenbogen BS: Impact of estrogen receptor β on gene networks regulated by estrogen receptor α in breast cancer cells. Endocrinol 2006;147:4831–4842.
  21. Zhao C, Wright KD, Gustafsson JA: Estrogen receptor β: an overview and update. Nucl Recept Signal 2008;6:1621–1721.
  22. Schmidt S, Michna H, Diel P: Combinatory effects of phytoestrogens and 17β estradiol on proliferation and apoptosis in MCF-7 breast cancer cells. J Steroid Biochem Mol Biol 2005;94:445–449.
  23. Jeune MAL, Diaka JK, Brown J: Anticancer activities of pomegranate extracts and genistein in human breast cancer cells. J Med Food 2005;8:469–475.
  24. Shaaban AM, Green AR, Karthik S, Alizadeh Y, Hughes TA, Harkins L, Ellis IO, Robertson JF, Paish EC, Saunders PT, Groome NP, Speirs V: Nuclear and cytoplasmic expression of ERβ1, ERβ2 and ERβ5 identifies distinct prognostic outcome for breast cancer patients. Clin Cancer Res 2008;14:5228–5235.
  25. Skliris GP, Leygue E, Watson PH, Murphy LC: Estrogen receptor alpha negative breast cancer patients: estrogen receptor beta as a therapeutic agent. J Steroid Biochem Mol Biol 2008;109:1–10.

Pay-per-View Options
Direct payment This item at the regular price: USD 38.00
Payment from account With a Karger Pay-per-View account (down payment USD 150) you profit from a special rate for this and other single items.
This item at the discounted price: USD 26.50