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Molecules 2019, 24(6), 1027; https://doi.org/10.3390/molecules24061027

EGCG-Derivative G28 Shows High Efficacy Inhibiting the Mammosphere-Forming Capacity of Sensitive and Resistant TNBC Models

1
Perlmutter Cancer Center, NYU School of Medicine, 522 First Avenue, Smilow Research Building, Room 1104, New York, NY 10016, USA
2
New Therapeutic Targets Laboratory (TargetsLab)-Oncology Unit, Department of Medical Sciences, Faculty of Medicine, University of Girona, Emili Grahit 77, 17003 Girona, Spain
3
Product, Process and Production Engineering Research Group (GREP), Department of Mechanical Engineering and Industrial Construction, University of Girona, Maria Aurèlia Capmany 61, 17003 Girona, Spain
4
Laboratori d’Innovació en Processos i Productes de Síntesi Orgànica (LIPPSO), Department of Chemistry, University of Girona, Maria Aurèlia Capmany 69, 17003 Girona, Spain
*
Authors to whom correspondence should be addressed.
These authors contributed equally to this work.
Academic Editors: Margarida Castell Escuer and Mariona Camps-Bossacoma
Received: 15 January 2019 / Revised: 11 March 2019 / Accepted: 12 March 2019 / Published: 15 March 2019
(This article belongs to the Special Issue Natural Polyphenols and Health)
Full-Text   |   PDF [2849 KB, uploaded 15 March 2019]   |  
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Abstract

Recent studies showed that Fatty Acid Synthase (FASN), a lipogenic enzyme overexpressed in several carcinomas, plays an important role in drug resistance. Furthermore, the enrichment of Breast Cancer Stem Cell (BCSC) features has been found in breast tumors that progressed after chemotherapy. Hence, we used the triple negative breast cancer (TNBC) cell line MDA-MB-231 (231) to evaluate the FASN and BCSC population role in resistance acquisition to chemotherapy. For this reason, parental cell line (231) and its derivatives resistant to doxorubicin (231DXR) and paclitaxel (231PTR) were used. The Mammosphere-Forming Assay and aldehyde dehydrogenase (ALDH) enzyme activity assay showed an increase in BCSCs in the doxorubicin-resistant model. Moreover, the expression of some transcription factors involved in epithelial-mesenchymal transition (EMT), a process that confers BCSC characteristics, was upregulated after chemotherapy treatment. FASN inhibitors C75, (−)-Epigallocatechin 3-gallate (EGCG), and its synthetic derivatives G28, G56 and G37 were used to evaluate the effect of FASN inhibition on the BCSC-enriched population in our cell lines. G28 showed a noticeable antiproliferative effect in adherent conditions and, interestingly, a high mammosphere-forming inhibition capacity in all cell models. Our preliminary results highlight the importance of studying FASN inhibitors for the treatment of TNBC patients, especially those who progress after chemotherapy. View Full-Text
Keywords: FASN inhibition; triple-negative breast cancer; cancer stem cells; EGCG; G28; polyphenolic compound; fatty acid metabolism FASN inhibition; triple-negative breast cancer; cancer stem cells; EGCG; G28; polyphenolic compound; fatty acid metabolism
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Giró-Perafita, A.; Rabionet, M.; Planas, M.; Feliu, L.; Ciurana, J.; Ruiz-Martínez, S.; Puig, T. EGCG-Derivative G28 Shows High Efficacy Inhibiting the Mammosphere-Forming Capacity of Sensitive and Resistant TNBC Models. Molecules 2019, 24, 1027.

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