SERPINB3 protects from oxidative damage by chemotherapeutics through inhibition of mitochondrial respiratory complex I

• DOI: 10.18632/oncotarget.1411
• Publication Date: 2015-09-15T23:40:12Z
• Authors: Francesco Ciscato; Marco Sciacovelli; Gianmarco Villano; Cristian Turato; Paolo Bernardi; Andrea Rasola; Patrizia Pontisso
• Keywords: 0301 basic medicine; Carcinoma, Hepatocellular; Blotting, Western; 610; Antineoplastic Agents; Apoptosis; Mitochondrial Membrane Transport Proteins; respiratory complexes; 03 medical and health sciences; Antigens, Neoplasm; Tumor Cells, Cultured; SERPINB3; Humans; Immunoprecipitation; Calcium Signaling; Serpins; Cell Proliferation; reactive oxygen species; Electron Transport Complex I; Mitochondrial Permeability Transition Pore; chemotherapeutics; Liver Neoplasms; Mitochondria; 3. Good health; mitochondria; Oxidative Stress; cell death; Drug Resistance, Neoplasm; Reactive Oxygen Species; Oxidation-Reduction

// Francesco Ciscato 1,2 Marco Sciacovelli 1,3 , Gianmarco Villano 2 Cristian Turato Paolo Bernardi 1 Andrea Rasola Patrizia Pontisso CNR Institute of Neuroscience and Department Biomedical Sciences, University Padova, Italy; Medicine, Italy 3 present address: Medical Research Council Cancer Unit, Hutchison/MRC Centre, Hills Road, Cambridge, United Kingdom Correspondence: Rasola, email: Keywords : SERPINB3; chemotherapeutics; mitochondria; respiratory complexes; reactive oxygen species; cell death Received September 13, 2013 Accepted December 24, Published Abstract SERPINB3 (SB3) is a serine protease inhibitor overexpressed in several malignancies epithelial origin, including primary liver cancer, where it inhibits apoptosis through poorly defined mechanisms. In the study we analyze effect SB3 on hepatoma elicited by panel chemotherapeutic agents. We report that shields cells from toxicity drugs with pro-oxidant action such as doxorubicin, cisplatin EM20-25. The rapid rise ROS levels prompted these compounds causes opening mitochondrial permeability transition pore (PTP), irreversibly committing to death. find fraction locates inner compartments, this increases under conditions oxidative stress. Mitochondrial generation ensuing PTP induction an inhibitory interaction Complex I. These findings identify novel mechanism contributes tumor resistance anti-neoplastic