(−)-Epigallocatechin 3-Gallate Synthetic Analogues Inhibit Fatty Acid Synthase and Show Anticancer Activity in Triple Negative Breast Cancer
Joan Crous-Masó,
Sònia Palomeras,
Joana Relat,
Cristina Camó,
Úrsula Martínez-Garza,
Marta Planas,
Lidia Feliu,
Teresa Puig
Affiliations
Joan Crous-Masó
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
Sònia Palomeras
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
Joana Relat
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
Cristina Camó
LIPPSO, Department of Chemistry, University of Girona, Maria Aurèlia Capmany 69, 17003 Girona, Spain
Úrsula Martínez-Garza
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
Marta Planas
LIPPSO, Department of Chemistry, University of Girona, Maria Aurèlia Capmany 69, 17003 Girona, Spain
Lidia Feliu
LIPPSO, Department of Chemistry, University of Girona, Maria Aurèlia Capmany 69, 17003 Girona, Spain
Teresa Puig
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
(−)-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.
