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.
Keywords: AMPK, aspirin, berberine, cancer therapy, metformin, resveratrol.
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