The multikinase inhibitor Sorafenib targets mitochondria and synergizes with glycolysis blockade for cancer cell killing.

ABSTRACT: Objective: identify novel and relevant aspects of Sorafenib action on liver cancer cells. We found that in rat hepatocholangiocarcinoma (LCSC-2) cells, exposure to the MEK/multikinase inhibitor sorafenib did not inhibit ERK phosphorylation nor induced appreciable cell death in the low micromolar range; instead, the drug elicited a raise of intracellular reactive oxygen species (ROS) accompanied by a severe decrease of oxygen consumption and intracellular ATP levels, all changes consistent with mitochondrial damage. Moreover, Sorafenib induced depolarization of isolated rat liver mitochondria, indicating a possible direct effect on the organelle. Microarray analysis of gene expression in sorafenib-trated cells revealed a metabolic reprogramming toward aerobic glycolysis, that likely accou

ORGANISM(S): Rattus norvegicus

SUBMITTER: camilla bernardini 

PROVIDER: E-GEOD-43053 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress