The soy isoflavone equol may increase cancer malignancy via up-regulation of eukaryotic protein synthesis initiation factor eIF4G.
Enviado por Michelle Martínez Montemayor el
Título | The soy isoflavone equol may increase cancer malignancy via up-regulation of eukaryotic protein synthesis initiation factor eIF4G. |
Publication Type | Journal Article |
Year of Publication | 2012 |
Autores | de la Parra, C, Otero-Franqui, E, Martinez-Montemayor, M, Dharmawardhane, S |
Journal | J Biol Chem |
Volume | 287 |
Issue | 50 |
Pagination | 41640-50 |
Date Published | 2012 Dec 7 |
ISSN | 1083-351X |
Palabras clave | Animals, Breast Neoplasms, Cell Line, Tumor, Dietary Supplements, Equol, Eukaryotic Initiation Factor-4E, Eukaryotic Initiation Factor-4G, Female, Gene Expression Regulation, Neoplastic, Humans, Isoflavones, Mice, Mice, Nude, Neoplasm Transplantation, Phytoestrogens, Protein Biosynthesis, Proto-Oncogene Proteins c-myc, RNA, Messenger, RNA, Neoplasm, Soybeans, Transplantation, Heterologous, Up-Regulation |
Abstract | Dietary soy is thought to be cancer-preventive; however, the beneficial effects of soy on established breast cancer is controversial. We recently demonstrated that dietary daidzein or combined soy isoflavones (genistein, daidzein, and glycitein) increased primary mammary tumor growth and metastasis. Cancer-promoting molecules, including eukaryotic protein synthesis initiation factors (eIF) eIF4G and eIF4E, were up-regulated in mammary tumors from mice that received dietary daidzein. Herein, we show that increased eIF expression in tumor extracts of mice after daidzein diets is associated with protein expression of mRNAs with internal ribosome entry sites (IRES) that are sensitive to eIF4E and eIF4G levels. Results with metastatic cancer cell lines show that some of the effects of daidzein in vivo can be recapitulated by the daidzein metabolite equol. In vitro, equol, but not daidzein, up-regulated eIF4G without affecting eIF4E or its regulator, 4E-binding protein (4E-BP), levels. Equol also increased metastatic cancer cell viability. Equol specifically increased the protein expression of IRES containing cell survival and proliferation-promoting molecules and up-regulated gene and protein expression of the transcription factor c-Myc. Moreover, equol increased the polysomal association of mRNAs for p 120 catenin and eIF4G. The elevated eIF4G in response to equol was not associated with eIF4E or 4E-binding protein in 5' cap co-capture assays or co-immunoprecipitations. In dual luciferase assays, IRES-dependent protein synthesis was increased by equol. Therefore, up-regulation of eIF4G by equol may result in increased translation of pro-cancer mRNAs with IRESs and, thus, promote cancer malignancy. |
DOI | 10.1074/jbc.M112.393470 |
Alternate Journal | J. Biol. Chem. |
PubMed ID | 23095751 |
PubMed Central ID | PMC3516715 |
Grant List | G12 MD007583 / MD / NIMHD NIH HHS / United States G12 RR003035 / RR / NCRR NIH HHS / United States G12RR003035 / RR / NCRR NIH HHS / United States G12RR035051 / RR / NCRR NIH HHS / United States SC3 GM084824 / GM / NIGMS NIH HHS / United States SC3GM084824 / GM / NIGMS NIH HHS / United States |