Individual and combined soy isoflavones exert differential effects on metastatic cancer progressionReport as inadecuate

Individual and combined soy isoflavones exert differential effects on metastatic cancer progression - Download this document for free, or read online. Document in PDF available to download.

Clinical and Experimental Metastasis

, Volume 27, Issue 7, pp 465–480

First Online: 02 June 2010Received: 05 February 2010Accepted: 12 May 2010DOI: 10.1007-s10585-010-9336-x

Cite this article as: Martínez-Montemayor, M.M., Otero-Franqui, E., Martinez, J. et al. Clin Exp Metastasis 2010 27: 465. doi:10.1007-s10585-010-9336-x


To investigate the effects soy isoflavones in established cancers, the role of genistein, daidzein, and combined soy isoflavones was studied on progression of subcutaneous tumors in nude mice created from green fluorescent protein GFP tagged-MDA-MB-435 cells. Following tumor establishment, mice were gavaged with vehicle or genistein or daidzein at 10 mg-kg body weight BW or a combination of genistein 10 mg-kg BW, daidzein 9 mg-kg BW, and glycitein 1 mg-kg BW three times per week. Tumor progression was quantified by whole body fluorescence image analysis followed by microscopic image analysis of excised organs for metastases. Results show that daidzein increased while genistein decreased mammary tumor growth by 38 and 33% respectively, compared to vehicle. Daidzein increased lung and heart metastases while genistein decreased bone and liver metastases. Combined soy isoflavones did not affect primary tumor growth but increased metastasis to all organs tested, which include lung, liver, heart, kidney, and bones. Phosphoinositide-3-kinase PI3-K pathway real time PCR array analysis and western blotting of excised tumors demonstrate that genistein significantly downregulated 10-84 genes, including the Rho GTPases RHOA, RAC1, and CDC42 and their effector PAK1. Daidzein significantly upregulated 9-84 genes that regulate proliferation and protein synthesis including EIF4G1, eIF4E, and survivin protein levels. Combined soy treatment significantly increased gene and protein levels of EIF4E and decreased TIRAP gene expression. Differential regulation of Rho GTPases, initiation factors, and survivin may account for the disparate responses of breast cancers to genistein and daidzein diets. This study indicates that consumption of soy foods may increase metastasis.

KeywordsGenistein Daidzein Glycitein Cancer metastasis Soy isoflavones Electronic supplementary materialThe online version of this article doi:10.1007-s10585-010-9336-x contains supplementary material, which is available to authorized users.

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Author: Michelle M. Martínez-Montemayor - Elisa Otero-Franqui - Joel Martinez - Alina De La Mota-Peynado - Luis A. Cubano - Surang


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