New Approach for Treatment of Primary Liver Tumors: The Role of Quercetin.

Autor: Brito AF; a Biophysics and Biomathematics Institute, IBILI-Faculty of Medicine, University of Coimbra, Coimbra, Portugal.; b Center of Investigation on Environmental, Genetics and Oncobiology (CIMAGO), Faculty of Medicine, University of Coimbra , Coimbra , Portugal., Ribeiro M; a Biophysics and Biomathematics Institute, IBILI-Faculty of Medicine, University of Coimbra, Coimbra, Portugal.; c Faculty of Sciences and Technology, University of Coimbra , Coimbra , Portugal., Abrantes AM; a Biophysics and Biomathematics Institute, IBILI-Faculty of Medicine, University of Coimbra, Coimbra, Portugal.; b Center of Investigation on Environmental, Genetics and Oncobiology (CIMAGO), Faculty of Medicine, University of Coimbra , Coimbra , Portugal.; d CNC.IBILI, Faculty of Medicine, University of Coimbra , Coimbra , Portugal., Mamede AC; a Biophysics and Biomathematics Institute, IBILI-Faculty of Medicine, University of Coimbra, Coimbra, Portugal.; b Center of Investigation on Environmental, Genetics and Oncobiology (CIMAGO), Faculty of Medicine, University of Coimbra , Coimbra , Portugal.; d CNC.IBILI, Faculty of Medicine, University of Coimbra , Coimbra , Portugal.; e CICS-UBI, Health Sciences Research Centre, University of Beira Interior , Covilhã , Portugal., Laranjo M; a Biophysics and Biomathematics Institute, IBILI-Faculty of Medicine, University of Coimbra, Coimbra, Portugal.; b Center of Investigation on Environmental, Genetics and Oncobiology (CIMAGO), Faculty of Medicine, University of Coimbra , Coimbra , Portugal.; d CNC.IBILI, Faculty of Medicine, University of Coimbra , Coimbra , Portugal., Casalta-Lopes JE; a Biophysics and Biomathematics Institute, IBILI-Faculty of Medicine, University of Coimbra, Coimbra, Portugal.; b Center of Investigation on Environmental, Genetics and Oncobiology (CIMAGO), Faculty of Medicine, University of Coimbra , Coimbra , Portugal., Gonçalves AC; b Center of Investigation on Environmental, Genetics and Oncobiology (CIMAGO), Faculty of Medicine, University of Coimbra , Coimbra , Portugal.; d CNC.IBILI, Faculty of Medicine, University of Coimbra , Coimbra , Portugal.; f Applied Molecular Biology and Hematology Group, Faculty of Medicine, University of Coimbra , Coimbra , Portugal., Sarmento-Ribeiro AB; b Center of Investigation on Environmental, Genetics and Oncobiology (CIMAGO), Faculty of Medicine, University of Coimbra , Coimbra , Portugal.; d CNC.IBILI, Faculty of Medicine, University of Coimbra , Coimbra , Portugal.; f Applied Molecular Biology and Hematology Group, Faculty of Medicine, University of Coimbra , Coimbra , Portugal., Tralhão JG; a Biophysics and Biomathematics Institute, IBILI-Faculty of Medicine, University of Coimbra, Coimbra, Portugal.; b Center of Investigation on Environmental, Genetics and Oncobiology (CIMAGO), Faculty of Medicine, University of Coimbra , Coimbra , Portugal.; g Surgical Department , Surgery A, CHUC , Coimbra , Portugal., Botelho MF; a Biophysics and Biomathematics Institute, IBILI-Faculty of Medicine, University of Coimbra, Coimbra, Portugal.; b Center of Investigation on Environmental, Genetics and Oncobiology (CIMAGO), Faculty of Medicine, University of Coimbra , Coimbra , Portugal.; d CNC.IBILI, Faculty of Medicine, University of Coimbra , Coimbra , Portugal.
Jazyk: angličtina
Zdroj: Nutrition and cancer [Nutr Cancer] 2016; Vol. 68 (2), pp. 250-66. Date of Electronic Publication: 2016 Mar 04.
DOI: 10.1080/01635581.2016.1145245
Abstrakt: Hepatocellular carcinoma (HCC) is the most common primary liver tumor (PLT), with cholangiocarcinoma (CC) being the second most frequent. Glucose transporter 1 (GLUT-1) expression is increased in PLTs and therefore it is suggested as a therapeutic target. Flavonoids, like quercetin, are GLUT-1 competitive inhibitors and may be considered as potential therapeutic agents for PLTs. The objective of this study was evaluation of quercetin anticancer activity in three human HCC cell lines (HepG2, HuH7, and Hep3B2.1-7) and in a human CC cell line (TFK-1). The possible synergistic effect between quercetin and sorafenib, a nonspecific multikinase inhibitor used in clinical practice in patients with advanced HCC, was also evaluated. It was found that in all the cell lines, quercetin induced inhibition of the metabolic activity and cell death by apoptosis, followed by increase in BAX/BCL-2 ratio. Treatment with quercetin caused DNA damage in HepG2, Hep3B2.1-7, and TFK-1 cell lines. The effect of quercetin appears to be independent of P53. Incubation with quercetin induced an increase in GLUT-1 membrane expression and a consequent reduction in the cytoplasmic fraction, observed as a decrease in (18)F-FDG uptake, indicating a GLUT-1 competitive inhibition. The occurrence of synergy when sorafenib and quercetin were added simultaneously to HCC cell lines was noticed. Thus, the use of quercetin seems to be a promising approach for PLTs through GLUT-1 competitive inhibition.
Databáze: MEDLINE
Nepřihlášeným uživatelům se plný text nezobrazuje