title: Combined cancer therapy with non-conventional drugs: all roads lead to AMPK.
abstract: AMP-activated protein kinase (AMPK) is a key energy sensor that regulates cellular energy homeostasis. AMPK activation is associated with decreased phosphorylation of mammalian target of rapamycin (mTOR) and S6 kinase and causes a general reduction in mRNA translation and protein synthesis. Therefore, AMPK is a novel target for anticancer therapy. Metformin and aspirin are two traditional drugs that are widely used as anti-diabetes and non-steroidal anti-inflammatory drugs (NSAIDs), respectively. Much evidence has confirmed that these two drugs demonstrated encouraging anti-cancer properties. Most importantly, both inhibited tumor proliferation and were mainly dependent on the AMPK/mTOR signaling pathway. In addition, several other drugs, such as resveratrol, berberine, statins, epigallocatechin gallate (EGCG) and capsaicin, have provided a similar capacity for tumor inhibition, and the anti-cancer effects of most of them were mainly the result of AMPK activation. In the current review, we summarize the literature on combination therapy based on these non-classical drugs and their potential mechanisms for activating AMPK. Combinations of these drugs will provide a novel cancer therapeutic regimen.
authors.forename: Suning
authors.initials: S
authors.lastname: Chen
authors.forename: Xingmei
authors.initials: X
authors.lastname: Zhu
authors.forename: Xiaofeng
authors.initials: X
authors.lastname: Lai
authors.forename: Tian
authors.initials: T
authors.lastname: Xiao
authors.forename: Aidong
authors.initials: A
authors.lastname: Wen
authors.affiliation: State Key Laboratory of Cancer Biology, Department of Biochemistry and Molecular Biology, The Fourth Military Medical University, No. 169 Changle West Road, 710032, Xi'an, PR China. biozhangj@hotmail.com.
authors.forename: Jian
authors.initials: J
authors.lastname: Zhang
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000378:metabolism*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001241:Aspirin / Q000494:pharmacology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology; D008687:Metformin / Q000494:pharmacology; D009369:Neoplasms / Q000188:drug therapy*
chemical_list: D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D008687:Metformin; D055372:AMP-Activated Protein Kinases; D001241:Aspirin