title: Effect of sorafenib on the energy metabolism of hepatocellular carcinoma cells.
abstract: Recent data demonstrated that sorafenib impaired the oxidative phosphorylation of a rat myogenic cell line and suggested that this biochemical lesion can contribute to the cardiac toxicity caused by the drug. With the experiments reported here, we verified whether sorafenib inhibits oxidative phosphorylation also in cells from human hepatocellular carcinomas (HCCs), which are treated with this drug. By using the HCC cell lines PLC/PRF/5 and SNU-449 we studied the effects of the drug on ATP cellular levels, oxygen consumption and aerobic glycolysis, a metabolic pathway generally used by neoplastic cells to meet their energy demand. The effect of sorafenib on ATP cellular levels was also studied in cells grown in a glucose-free medium, which only derive their energy from oxidative phosphorylation. We found that at clinically relevant concentrations sorafenib hindered oxidative phosphorylation, whereas at the same time stimulated aerobic glycolysis in glucose-grown cells, thus attenuating the cellular ATP depletion. These results support the impairment of oxidative phosphorylation as a mechanism contributing to the antineoplastic activity of sorafenib in the treatment of HCCs.
authors.affiliation: Department of Experimental Pathology, University of Bologna, Italy.
authors.forename: Luigi
authors.initials: L
authors.lastname: Fiume
authors.forename: Marcella
authors.initials: M
authors.lastname: Manerba
authors.forename: Marina
authors.initials: M
authors.lastname: Vettraino
authors.forename: Giuseppina
authors.initials: G
authors.lastname: Di Stefano
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D000332:Aerobiosis / Q000187:drug effects; D000970:Antineoplastic Agents / Q000494:pharmacology*; D001557:Benzenesulfonates / Q000494:pharmacology*; D006528:Carcinoma, Hepatocellular / Q000378:metabolism* / Q000473:pathology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D019069:Cell Respiration / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D004734:Energy Metabolism / Q000187:drug effects*; D006031:Glycosylation / Q000187:drug effects; D006801:Humans; D008113:Liver Neoplasms / Q000378:metabolism* / Q000473:pathology*; D009536:Niacinamide / Q000031:analogs & derivatives; D010085:Oxidative Phosphorylation / Q000187:drug effects; D010671:Phenylurea Compounds; D011725:Pyridines / Q000494:pharmacology*; D000077157:Sorafenib
chemical_list: D000970:Antineoplastic Agents; D001557:Benzenesulfonates; D010671:Phenylurea Compounds; D011725:Pyridines; D009536:Niacinamide; D000255:Adenosine Triphosphate; D000077157:Sorafenib