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Metabolomic Response to Sorafenib Treatment in Human Hepatocellular Carcinoma Cells
Author(s) -
Zhou Shufeng,
Luo Ruijuan
Publication year - 2013
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.27.1_supplement.663.7
Subject(s) - sorafenib , metabolomics , hepatocellular carcinoma , pharmacology , metabolic pathway , drug , drug metabolism , mechanism (biology) , cancer research , computational biology , biology , chemistry , bioinformatics , metabolism , biochemistry , philosophy , epistemology
Untargeted metabolomics has enabled comprehensive overview on physiological system and provides chances for new discoveries linking cellular pathways to biological mechanism, which also is a good platform for better understanding of drug action. In this study, we employed a metabolomics method to examine how the multikinase inhibitor sorafenib affects metabolic pathways in human hepatocellular carcinoma cell line. The results showed that sorafenib treatment in HepG2 cells caused remarkable changes of several metabolic pathways in a concentration‐dependent manner. At a low concentration of sorafenib, the glycerophospholipid metabolism was the most affected pathway, while at a higher concentration, the purine metabolism was most significantly altered. The significant decrease of GTP level after sorafenib treatment could be associated with the toxicity of this drug. These findings have provided insights into how sorafenib acts on distinct metabolic and biochemical pathways that are associated with its therapeutic efficacy and side effects. Metabolic profiling studies for clinically approved kinase inhibitors can serve as a powerful tool to facilitate the understanding of their mechanism of actions, molecular targets and the interactome.