title: Quercetin and epigallocatechin gallate inhibit glucose uptake and metabolism by breast cancer cells by an estrogen receptor-independent mechanism.
abstract: In this study we characterized (3)H-2-deoxy-d-glucose ((3)H -DG) uptake by the estrogen receptor (ER)-positive MCF7 and the ER-negative MDA-MB-231 human breast cancer cell lines and investigated the effect of quercetin (QUE) and epigallocatechin gallate (EGCG) upon (3)H-DG uptake, glucose metabolism and cell viability and proliferation. In both MCF7 and MDA-MB-231 cells (3)H-DG uptake was (a) time-dependent, (b) saturable with similar capacity (Vmax) and affinity (Km), (c) potently inhibited by cytochalasin B, an inhibitor of the facilitative glucose transporters (GLUT), (d) sodium-independent and (e) slightly insulin-stimulated. This suggests that (3)H-DG uptake by both cell types is mediated by members of the GLUT family, including the insulin-responsive GLUT4 or GLUT12, while being independent of the sodium-dependent glucose transporter (SGLT1). QUE and EGCG markedly and concentration-dependently inhibited (3)H-DG uptake by MCF7 and by MDA-MB-231 cells, and both compounds blocked lactate production by MCF7 cells. Additionally, a 4h-treatment with QUE or EGCG decreased MCF7 cell viability and proliferation, an effect that was more potent when glucose was available in the extracellular medium. Our results implicate QUE and EGCG as metabolic antagonists in breast cancer cells, independently of estrogen signalling, and suggest that these flavonoids could serve as therapeutic agents/adjuvants even for ER-negative breast tumors.
authors.affiliation: Department of Biochemistry (U38-FCT), Faculty of Medicine of University of Porto, Alameda Prof. Hernâni Monteiro, 4200-319 Porto, Portugal. Electronic address: lilianam87@gmail.com.
authors.forename: Liliana
authors.initials: L
authors.lastname: Moreira
authors.affiliation: Department of Biochemistry (U38-FCT), Faculty of Medicine of University of Porto, Alameda Prof. Hernâni Monteiro, 4200-319 Porto, Portugal. Electronic address: isa.araujo013@gmail.com.
authors.forename: Isabel
authors.initials: I
authors.lastname: Araújo
authors.affiliation: Department of Biochemistry (U38-FCT), Faculty of Medicine of University of Porto, Alameda Prof. Hernâni Monteiro, 4200-319 Porto, Portugal. Electronic address: tito.fmup16@gmail.com.
authors.forename: Tito
authors.initials: T
authors.lastname: Costa
authors.affiliation: Department of Biochemistry (U38-FCT), Faculty of Medicine of University of Porto, Alameda Prof. Hernâni Monteiro, 4200-319 Porto, Portugal. Electronic address: ana.clmc.branco@gmail.com.
authors.forename: Ana
authors.initials: A
authors.lastname: Correia-Branco
authors.affiliation: Department of Biochemistry (U38-FCT), Faculty of Medicine of University of Porto, Alameda Prof. Hernâni Monteiro, 4200-319 Porto, Portugal; Chemistry Investigation Centre (CIQ), Faculty of Sciences of University of Porto, Rua Campo Alegre, 4169-007 Porto, Portugal; Faculty of Nutrition and Food Sciences of University of Porto, Rua Dr. Roberto Frias, 4200-465 Porto, Portugal. Electronic address: anafaria@med.up.pt.
authors.forename: Ana
authors.initials: A
authors.lastname: Faria
authors.affiliation: Department of Biochemistry (U38-FCT), Faculty of Medicine of University of Porto, Alameda Prof. Hernâni Monteiro, 4200-319 Porto, Portugal. Electronic address: fmartel@med.up.pt.
authors.forename: Fátima
authors.initials: F
authors.lastname: Martel
authors.affiliation: Department of Biochemistry (U38-FCT), Faculty of Medicine of University of Porto, Alameda Prof. Hernâni Monteiro, 4200-319 Porto, Portugal. Electronic address: keating@med.up.pt.
authors.forename: Elisa
authors.initials: E
authors.lastname: Keating
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D001943:Breast Neoplasms / Q000378:metabolism*; D002277:Carcinoma / Q000378:metabolism; D002392:Catechin / Q000031:analogs & derivatives* / Q000494:pharmacology; D016923:Cell Death / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D005260:Female; D005947:Glucose / Q000378:metabolism*; D006801:Humans; D019344:Lactic Acid / Q000378:metabolism; D061986:MCF-7 Cells; D011794:Quercetin / Q000494:pharmacology*; D011960:Receptors, Estrogen / Q000235:genetics / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; D011960:Receptors, Estrogen; D019344:Lactic Acid; D002392:Catechin; D011794:Quercetin; C045651:epigallocatechin gallate; D005947:Glucose