Individual and combined soy isoflavones exert differential effects on metastatic cancer progression.

Imagen de Michelle Martínez Montemayor
PDF versionPDF version
TítuloIndividual and combined soy isoflavones exert differential effects on metastatic cancer progression.
Publication TypeJournal Article
Year of Publication2010
AutoresMartínez-Montemayor, MM, Otero-Franqui, E, Martinez, J, De La Mota-Peynado, A, Cubano, LA, Dharmawardhane, S
JournalClin Exp Metastasis
Volume27
Issue7
Pagination465-80
Date Published2010 Oct
ISSN1573-7276
Palabras claveAnimals, Blotting, Western, Cell Line, Tumor, Disease Progression, Female, Genistein, Humans, Isoflavones, Mice, Mice, Nude, Neoplasm Metastasis, Neoplasm Transplantation, Reverse Transcriptase Polymerase Chain Reaction, Soybeans
Abstract

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.

DOI10.1007/s10585-010-9336-x
Alternate JournalClin. Exp. Metastasis
PubMed ID20517637
PubMed Central IDPMC2944964
Grant ListG12 MD007583 / MD / NIMHD NIH HHS / United States
G12 RR003035 / RR / NCRR NIH HHS / United States
G12RR003035 / RR / NCRR NIH HHS / United States
S06GM050695 / GM / NIGMS NIH HHS / United States
SC3 GM084824-02 / GM / NIGMS NIH HHS / United States
SC3 GM084824-04 / GM / NIGMS NIH HHS / United States
SC3GM084824 / GM / NIGMS NIH HHS / United States