Regorafenib impairs mitochondrial functions, activates AMP-activated protein kinase, induces autophagy, and causes rat hepatocyte necrosis

Highlights • Regorafenib uncouples hepatic mitochondrial oxidative phosphorylation. • Regorafenib causes necrosis but not apoptosis in hepatocytes. • Regorafenib activates AMP-activated protein kinase and autophagy. • Regorafenib cytotoxicity is observed at clinically relevant concentrations....

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Bibliographic Details
Published in:	Toxicology (Amsterdam) Vol. 327; no. C; pp. 10 - 21
Main Authors:	Weng, Zuquan, Luo, Yong, Yang, Xi, Greenhaw, James J, Li, Haibo, Xie, Liming, Mattes, William B, Shi, Qiang
Format:	Journal Article
Language:	English
Published:	Ireland Elsevier B.V 02-01-2015 Elsevier
Subjects:	Activation AMP-Activated Protein Kinases - metabolism Animals ATP Autophagy - drug effects Emergency Enzyme Activation Fructose Hepatocyte Hepatocytes - cytology Hepatocytes - drug effects Hepatotoxicity Inhibitors Kinases Male Mitochondria Mitochondria, Liver - drug effects Mitochondria, Liver - physiology Mitochondrion Necrosis Phenylurea Compounds - pharmacology Pyridines - pharmacology Rat Rats Rats, Sprague-Dawley Regorafenib Shortages Toxicity Mitochondrion Regorafenib Rat Hepatocyte Hepatotoxicity Necrosis
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Summary:	Highlights • Regorafenib uncouples hepatic mitochondrial oxidative phosphorylation. • Regorafenib causes necrosis but not apoptosis in hepatocytes. • Regorafenib activates AMP-activated protein kinase and autophagy. • Regorafenib cytotoxicity is observed at clinically relevant concentrations.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 USDOE
ISSN:	0300-483X 1879-3185
DOI:	10.1016/j.tox.2014.11.002