Abstract
Continuing efforts are directed towards finding alternative breast cancer chemotherapeutics, with improved safety and efficacy profiles. Soy isoflavones represent promising agents but, despite extensive research, limited information exists regarding their impact on the breast cancer cell proteome. The purpose of this study was to compare the proteomic profiles of MCF-7 (estrogen responsive) and MDA-MB-231 (estrogen non-responsive) breast cancer cells exposed to different concentrations of genistein, daidzein, and a soy seed extract, using a high throughput LC–UDMSE protein profiling approach. The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay confirmed the dual activity of soy isoflavones on MCF-7 cells and the inhibitory effect on MDA-MB-231 cells. Proteome profiling of paramagnetic beads prepared peptides by nano-LC UDMSE and pathway enrichment analysis revealed that isoflavones affected distinct molecular pathways in MCF-7 and MDA-MB-231 cells, such as tyrosine kinases signaling pathway, cytoskeleton organization, lipid and phospholipid catabolism, extracellular matrix degradation and mRNA splicing. Also, in MCF-7 cells, low and high isoflavone doses induced different changes of the proteome, including cell cycle alterations. Therefore, the expression of estrogen receptors and the isoflavone dose are determinant factors for the molecular impact of isoflavones and must be taken into account when considering adjuvant breast cancer therapy towards personalized medicine.
Highlights
Breast cancer is the most frequent malignancy among women and the second most common cancer amongst both sexes [1,2]
The purpose of this study was to compare the proteomic profiles of MCF-7 and MDA-MB-231 breast cancer cells exposed to different concentrations of genistein, daidzein, and a soy seed extract, using a high throughput LC–UDMSE protein profiling approach
We explored the proteomic profiles of two different breast cancer cells, MCF-7 and MDA-MB-231, exposed to different concentrations of Gen, Dai, and an soy seed extract (SSE)
Summary
Breast cancer is the most frequent malignancy among women and the second most common cancer amongst both sexes [1,2]. Perhaps one of the most characteristic feature of breast cancer is its molecular, phenotypic, and functional diversity, known as tumor heterogeneity, which challenges both prognosis and therapeutic strategies. The molecular features typically used for breast tumor subtyping include expression of the estrogen receptor (ER) and the progesterone receptor (PR), activation of human epidermal growth factor receptor 2 (HER2/neu, encoded by ERBB2), and/or the presence of BRCA1/2 mutations [3,4]. Chemotherapy has brought major improvements in controlling cancer’s progression, the treatment of breast cancer by means of chemotherapy is often accompanied by toxic side effects on the nontumoral tissues. Continuing efforts are directed towards finding alternative anticancer agents, with improved safety and efficacy profiles [5]
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