CIBICI   14215
CENTRO DE INVESTIGACION EN BIOQUIMICA CLINICA E INMUNOLOGIA
Unidad Ejecutora - UE
congresos y reuniones científicas
Título:
SUPPRESSION OF STARD7 DECREASES ABCG2 AND ENHANCES SENSITIVITY TO CHEMOTHERAPY DRUGS IN HUMAN CANCER
Autor/es:
FLORES-MARTÍN, JÉSICA; REYNA LUCIANA; RIDANO, MAGALÍ; PANZETTA DE DUTARI GRACIELA; GENTI DE RAIMONDI SUSANA
Lugar:
Rosario
Reunión:
Congreso; 50th Annual Meeting Argentine Society for Biochemistry and Molecular Biology; 2014
Institución organizadora:
SAIB
Resumen:
Drug resistance during chemotherapy is the major obstacle to the successful treatment of many cancers. Several ABC transporters have been recognized as a source of drug resistance in the treatment of malignancies. StarD7 is a member of the START domain superfamily, which is involved in lipid transfer, metabolism, and modulation of signaling pathways. Previous results indicate that StarD7 silencing decreases ABCG2 multidrug transporter level, cell migration, proliferation, and phospholipid synthesis; whereas an increase in biochemical and morphological differentiation marker expression was detected in the choriocarcinoma JEG-3 cells. Here, we report that inhibition of StarD7 by siRNA led to a marked decrease of ABCG2 expression in HepG2 and A549 cell lines. Using flow cytometry and a microplate reader assay, we found that intracellular accumulation of the chemotherapeutic agent mitoxantrone was enhanced in cell lines transfected with StarD7 siRNA. In addition, StarD7 silencing led to increased ROS basal level as well as ROS-mediated cell toxicity induced by H2O2. More importantly, knocking down StarD7 resulted in enhanced sensitivity of cancer cells to chemotherapeutic agents. In summary, our resultssuggest that targeted inhibition of StarD7 may be a novel therapeutic approach to overcome chemoresistance of epithelial cancer cells.