Suning Chen, Xingmei Zhu, Xiaofeng Lai, Tian Xiao, Aidong Wen and Jian Zhang Pages 642 - 654 ( 13 )
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.
AMPK, aspirin, berberine, cancer therapy, metformin, resveratrol.
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.