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Molecules 2018, 23(5), 1160; https://doi.org/10.3390/molecules23051160

(−)-Epigallocatechin 3-Gallate Synthetic Analogues Inhibit Fatty Acid Synthase and Show Anticancer Activity in Triple Negative Breast Cancer

1
New Therapeutic Targets Laboratory (Targets Lab)-Oncology Unit, Department of Medical Sciences, University of Girona, Girona Institute for Biomedical Research, Emili Grahit 77, 17003 Girona, Spain
2
LIPPSO, Department of Chemistry, University of Girona, Maria Aurèlia Capmany 69, 17003 Girona, Spain
3
Department of Nutrition, Food Sciences and Gastronomy, School of Pharmacy and Food Sciences, Food and Nutrition Torribera Campus, University of Barcelona, Prat de la Riba 171, 08921 Santa Coloma de Gramenet, Spain
4
Institute of Nutrition and Food Safety of the University of Barcelona (INSA-UB), Prat de la Riba 171, 08921 Santa Coloma de Gramenet, Spain
These authors contributed equally to this work.
*
Authors to whom correspondence should be addressed.
Received: 4 April 2018 / Revised: 2 May 2018 / Accepted: 10 May 2018 / Published: 11 May 2018
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Abstract

(−)-Epigallocatechin 3-gallate (EGCG) is a natural polyphenol from green tea with reported anticancer activity and capacity to inhibit the lipogenic enzyme fatty acid synthase (FASN), which is overexpressed in several human carcinomas. To improve the pharmacological profile of EGCG, we previously developed a family of EGCG derivatives and the lead compounds G28, G37 and G56 were characterized in HER2-positive breast cancer cells overexpressing FASN. Here, diesters G28, G37 and G56 and two G28 derivatives, monoesters M1 and M2, were synthesized and assessed in vitro for their cytotoxic, FASN inhibition and apoptotic activities in MDA-MB-231 triple-negative breast cancer (TNBC) cells. All compounds displayed moderate to high cytotoxicity and significantly blocked FASN activity, monoesters M1 and M2 being more potent inhibitors than diesters. Interestingly, G28, M1, and M2 also diminished FASN protein expression levels, but only monoesters M1 and M2 induced apoptosis. Our results indicate that FASN inhibition by such polyphenolic compounds could be a new strategy in TNBC treatment, and highlight the potential anticancer activities of monoesters. Thus, G28, G37, G56, and most importantly M1 and M2, are anticancer candidates (alone or in combination) to be further characterized in vitro and in vivo. View Full-Text
Keywords: triple-negative breast cancer; fatty acid synthase; FASN inhibition; polyphenolic FASN inhibitors; (−)-epigallocatechin 3-gallate; synthetic analogues; apoptosis; anticancer activity triple-negative breast cancer; fatty acid synthase; FASN inhibition; polyphenolic FASN inhibitors; (−)-epigallocatechin 3-gallate; synthetic analogues; apoptosis; anticancer activity
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Crous-Masó, J.; Palomeras, S.; Relat, J.; Camó, C.; Martínez-Garza, Ú.; Planas, M.; Feliu, L.; Puig, T. (−)-Epigallocatechin 3-Gallate Synthetic Analogues Inhibit Fatty Acid Synthase and Show Anticancer Activity in Triple Negative Breast Cancer. Molecules 2018, 23, 1160.

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