AMPK: A promising molecular target for combating cisplatin toxicities.

Abstract

Cisplatin is a broadly prescribed anti-tumor agent for the treatment of diverse cancers. Therapy with cisplatin, however, is associated with various adverse effects including nephrotoxicity and ototoxicity. AMP kinase (AMPK), an evolutionarily conserved enzyme, functions as the fundamental regulator of energy homeostasis. While AMPK activation protects normal tissues against cisplatin-induced toxicities, its impact in cancer is context-dependent and there is no single, uniform role for AMPK. On one hand, some report that AMPK activation augments cisplatin-induced apoptosis in cancer, while on the other hand, few reports indicate that AMPK activation rescues cancer cells from the cytotoxicity induced by cisplatin. Here we review the most salient signaling pathways regulated by AMPK with an emphasis on their relation to cisplatin toxicity and yet discuss context-dependent functions of AMPK in cancer.

• Authors: Nadereh Rashtchizadeh, Hassan Argani, Amir Ghorbanihaghjo, Davoud Sanajou, Vahid Hosseini, Siavoush Dastmalchi, Saeed Nazari Soltan Ahmad
• Journal: Biochemical pharmacology (Biochem Pharmacol) Vol. 163 Pg. 94-100 (05 2019) ISSN: 1873-2968 [Electronic] England
• PMID: 30738797 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Review)
• Copyright: Copyright © 2019 Elsevier Inc. All rights reserved.

Chemical References

• Antineoplastic Agents
• Protein Kinases
• AMP-Activated Protein Kinase Kinases
• Cisplatin

Topics

• AMP-Activated Protein Kinase Kinases
• Animals
• Antineoplastic Agents (toxicity)
• Cell Line, Tumor
• Cisplatin (toxicity)
• Drug Delivery Systems (methods, trends)
• Enzyme Activation (drug effects, physiology)
• Humans
• Neoplasms (drug therapy, enzymology)
• Protein Kinases (metabolism)
• Signal Transduction (drug effects, physiology)