Journal Article

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

Feliu, Lidia, Martínez Garza, Úrsula, Puig i Miquel, Teresa, Crous-Masó, Joan, Palomeras, Sonia, Planas, Marta, Camó, Cristina, Relat Pardo, Joana

2018

Overview

(􀀀)-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.

• Publisher: MDPI,MDPI AG,MDPI (Multidisciplinary Digital Publishing Institute)
• Subject: (−)-epigallocatechin 3-gallate / anticancer activity / apoptosis / Breast / Breast cancer / Cancer / Càncer / FASN inhibition / fatty acid synthase / Fatty acids / Mama / polyphenolic FASN inhibitors / synthetic analogues / triple-negative breast cancer