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Vol. 84, No. 2, 2009
Issue release date: August 2009
Pharmacology 2009;84:68–73
(DOI:10.1159/000226123)

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

Rajah T.T. · Du N. · Drews N. · Cohn R.
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Abstract

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.
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    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.
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  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.


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