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21.11.2018 | Original Contribution

Hydroxytyrosol inhibits cancer stem cells and the metastatic capacity of triple-negative breast cancer cell lines by the simultaneous targeting of epithelial-to-mesenchymal transition, Wnt/β-catenin and TGFβ signaling pathways

verfasst von: Marina Cruz-Lozano, Adrián González-González, Juan A. Marchal, Esperanza Muñoz-Muela, Maria P. Molina, Francisca E. Cara, Anthony M. Brown, Gerardo García-Rivas, Carmen Hernández-Brenes, Jose A. Lorente, Pedro Sanchez-Rovira, Jenny C. Chang, Sergio Granados-Principal

Erschienen in: European Journal of Nutrition | Ausgabe 8/2019

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Abstract

Purpose

This study was aimed to determine the impact of hydroxytyrosol (HT), a minor compound found in olive oil, on breast cancer stem cells (BCSCs) and the migration capacity of triple-negative breast cancer (TNBC) cell lines through the alteration of epithelial-to-mesenchymal transition (EMT) and embryonic signaling pathways.

Methods

BCSCs self-renewal was determined by the mammosphere-forming efficiency in SUM159PT, BT549, MDA-MB-231 and Hs578T TNBC cell lines. Flow cytometric analysis of CD44⁺/CD24^−/low and aldehyde dehydrogenase positive (ALDH⁺) subpopulations, migration by the “wound healing assay”, invasion and Western blot of EMT markers and TGFβ signaling were investigated in SUM159PT, BT549 and MDA-MB-231 cell lines. Wnt/β-catenin signaling was assessed by Western blot in BT549 cells expressing WNT1 and MDA-MB-231 cells. Changes in TGFβ activity was determined by SMAD Binding Element (SBE) reporter assay.

Results

HT reduced BCSCs self-renewal, ALDH⁺ (aldehyde dehydrogenase) and CD44⁺/CD24^−/low subpopulations, tumor cell migration and invasion. Consistently, HT suppressed Wnt/β-catenin signaling by decreasing p-LRP6, LRP6, β-catenin and cyclin D1 protein expression and the EMT markers SLUG, ZEB1, SNAIL and VIMENTIN. Finally, HT inhibited p-SMAD2/3 and SMAD2/3 in SUM159PT, BT549 and MDA-MB-231 cells, what was correlated with a less TGFβ activity.

Conclusion

In conclusion, we report for the first time the inhibitory role of HT on BCSCs and tumor cell migration by targeting EMT, Wnt/β-catenin and TGFβ signaling pathways. Our findings highlight the importance of the chemopreventive compound HT as a novel candidate to be investigated as an alternative targeted therapy for TNBC.

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Titel: Hydroxytyrosol inhibits cancer stem cells and the metastatic capacity of triple-negative breast cancer cell lines by the simultaneous targeting of epithelial-to-mesenchymal transition, Wnt/β-catenin and TGFβ signaling pathways
verfasst von: Marina Cruz-Lozano
Adrián González-González
Juan A. Marchal
Esperanza Muñoz-Muela
Maria P. Molina
Francisca E. Cara
Anthony M. Brown
Gerardo García-Rivas
Carmen Hernández-Brenes
Jose A. Lorente
Pedro Sanchez-Rovira
Jenny C. Chang
Sergio Granados-Principal
Publikationsdatum: 21.11.2018
Verlag: Springer Berlin Heidelberg
Erschienen in: European Journal of Nutrition / Ausgabe 8/2019
Print ISSN: 1436-6207
Elektronische ISSN: 1436-6215
DOI: https://doi.org/10.1007/s00394-018-1864-1

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Hydroxytyrosol inhibits cancer stem cells and the metastatic capacity of triple-negative breast cancer cell lines by the simultaneous targeting of epithelial-to-mesenchymal transition, Wnt/β-catenin and TGFβ signaling pathways

Abstract

Purpose

Methods

Results

Conclusion

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