Effect of sorafenib on the energy metabolism of hepatocellular carcinoma cells

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• 作者：Luigi Fiume ; Marcella Manerba ; Marina Vettraino ; Giuseppina Di Stefano ; ^{giuseppina.distefano@unibo.it}
• 关键词：Sorafenib ; Hepatocellular carcinoma chemotherapy ; Aerobic glycolysis ; Tumor cell metabolism
• 刊名：European Journal of Pharmacology
• 出版年：2011
• 出版时间：16 November, 2011
• 年：2011
• 卷：670
• 期：1
• 页码：39-43
• 全文大小：1K

文摘

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.