Journal article
Ailed M Cruz-Collazo, C. Parra, R. Schneider, Suranganie Marie Dharmawardhane
2017
2017
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APA
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Cruz-Collazo, A. M., Parra, C., Schneider, R., & Dharmawardhane, S. M. (2017). Protein Synthesis Regulation by Soy Isoflavones Metabolite Equol in Metastatic Breast Cancer Cells.
Chicago/Turabian
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Cruz-Collazo, Ailed M, C. Parra, R. Schneider, and Suranganie Marie Dharmawardhane. “Protein Synthesis Regulation by Soy Isoflavones Metabolite Equol in Metastatic Breast Cancer Cells” (2017).
MLA
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Cruz-Collazo, Ailed M., et al. Protein Synthesis Regulation by Soy Isoflavones Metabolite Equol in Metastatic Breast Cancer Cells. 2017.
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@article{ailed2017a,
title = {Protein Synthesis Regulation by Soy Isoflavones Metabolite Equol in Metastatic Breast Cancer Cells},
year = {2017},
author = {Cruz-Collazo, Ailed M and Parra, C. and Schneider, R. and Dharmawardhane, Suranganie Marie}
}
Abstract
Equol, one of the most studied metabolites of the soy isoflavone daidzein, is associated with both anticancer and pro‐cancer effects in breast cancer. These contradictory results have been shown to be concentration dependent, where high equol concentrations reduced non‐metastatic breast cancer cell growth and proliferation, and reduced breast cancer risk. However, we have shown that at low physiological dietary concentrations, equol increases cell proliferation, tumor growth and metastasis in metastatic breast cancer cell models. Also, equol increases the expression of the eukaryotic initiation factor 4G (eIF4G), increasing the cap‐independent protein synthesis of pro‐cancer molecules (de la Parra et al., J Biol Chem. 2012, 287(50):41640–50 and J Biol Chem. 2015, 290(10):6047–57). To elucidate the role of equol in the regulation of protein synthesis in metastatic breast cancer cells, a polysome profile assay using an Affymetrix microarray was conducted in cells treated with the following experimental conditions: vehicle control, equol, eIF4G knockdown (kd), or both equol + eIF4G kd. The following equation was used to identify the mRNAs that were actively translated for each experimental condition: [(mRNA associated with heavy or light polysome fraction/total mRNA)/(control mRNA associated with heavy or light polysome fraction/total control mRNA)]. This analysis using a false discovery rate (FDR) of <0.05 demonstrated that >1000 protein coding and non‐coding RNAs were differentially associated with polysomes in response to equol or eIF4G kd, but not for the combined treatment of equol + eIF4G kd. Ingenuity Pathway Analysis for mRNAs with a log2 fold change >2, demonstrated significant changes in mRNAs of cancer invasion proteins like MMP1, chromatin remodeling proteins like Histones, and cancer‐associated microRNAs (miRNAs) like miR21 and miR590. Therefore, our data has identified critical targets of equol involved in breast cancer metastasis regulation that are differentially expressed via translational control.
