Quercetin blocks the aggressive phenotype of triple-negative breast cancer by inhibiting igf1/ igf1r-mediated emt program
Journal
Journal of Food and Drug Analysis
Journal Volume
29
Journal Issue
1
Pages
98-112
Date Issued
2021
Author(s)
Abstract
The cancer-preventive activities of quercetin have been extensively studied in invasive breast cancer; however, the role of quercetin on triple-negative breast cancer (TNBC) with overexpression of insulin-like growth factor-1 receptor (IGF1R) has not been resolved. In this article, we demonstrated that quercetin inhibited the activation of IGF1R and its downstream kinases Akt and Erk1/2 in a dose-dependent manner in human MDA-MB-231 breast cancer cells (TNBC cell line). Related to this, quercetin markedly suppressed the metastatic phenotype and epithelialemesenchymal transition (EMT) of MDA-MB-231 cells by inhibiting the expression of EMT transcription factors Snail and Slug. Quercetin also increased the secretion of IGF-binding protein-3 in the conditioned medium of MDA-MB-231 cells while reducing the secretion of IGF1; thus, quercetin interrupted the autocrine or paracrine loop of IGF1 signaling. In xenograft mouse models, the administration of quercetin blocked the growth of MDA-MB-231 tumor xenografts and their lung metastasis, accompanied by the inactivation of IGF1R and the downregulation of the expression of Snail, Slug, and mesenchymal markers fibronectin and vimentin. These results suggest that quercetin has cancer-preventive value for TNBC by inhibiting IGF1/IGF1R signaling and preventing the consequent EMT and metastasis of TNBC. ? 2021, Taiwan Food and Drug Administration. All rights reserved.
Subjects
antineoplastic agent; cytokeratin 18; cytokeratin 19; fibronectin; mitogen activated protein kinase 1; mitogen activated protein kinase 3; protein kinase B; quercetin; somatomedin C; somatomedin C receptor; transcription factor Slug; transcription factor Snail; vimentin; animal experiment; animal model; animal tissue; antineoplastic activity; Article; autocrine signaling; carcinogenesis; cell motility; chemoluminescence; controlled study; down regulation; epithelial mesenchymal transition; female; fluorescence imaging; human; human cell; immunohistochemistry; in vitro study; lung metastasis; lung nodule; lung parenchyma; MCF-7 cell line; MDA-MB-231 cell line; mRNA expression level; nonhuman; paracrine signaling; phenotype; protein expression; protein secretion; rat; signal transduction; triple negative breast cancer; tumor growth; tumor invasion; tumor weight; tumor xenograft; Western blotting; wound healing assay
SDGs
Other Subjects
antineoplastic agent; cytokeratin 18; cytokeratin 19; fibronectin; mitogen activated protein kinase 1; mitogen activated protein kinase 3; protein kinase B; quercetin; somatomedin C; somatomedin C receptor; transcription factor Slug; transcription factor Snail; vimentin; animal experiment; animal model; animal tissue; antineoplastic activity; Article; autocrine signaling; carcinogenesis; cell motility; chemoluminescence; controlled study; down regulation; epithelial mesenchymal transition; female; fluorescence imaging; human; human cell; immunohistochemistry; in vitro study; lung metastasis; lung nodule; lung parenchyma; MCF-7 cell line; MDA-MB-231 cell line; mRNA expression level; nonhuman; paracrine signaling; phenotype; protein expression; protein secretion; rat; signal transduction; triple negative breast cancer; tumor growth; tumor invasion; tumor weight; tumor xenograft; Western blotting; wound healing assay
Type
journal article