Combined Cancer Therapy with Non-Conventional Drugs: all Roads Lead to AMPK.

Mini Rev Med Chem. 2014 Aug 19. [Epub ahead of print]
Combined Cancer Therapy with Non-Conventional Drugs: all Roads Lead to AMPK.

1The 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.

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 anti-cancer 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,C, 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.

PMID:25138094      [PubMed – as supplied by publisher]

Repurposing of metformin and aspirin by targeting AMPK-mTOR and inflammation for pancreatic cancer prevention and treatment.

Cancer Prev Res (Phila). 2014 Feb 11. [Epub ahead of print]
Repurposing of metformin and aspirin by targeting AMPK-mTOR and inflammation for pancreatic cancer prevention and treatment.

1Medicine/Population Science, Rutgers Cancer Insititue of New Jersey.

Abstract

Pancreatic cancer, as the fourth leading cause of cancer-related deaths, carries a poor prognosis with a median survival of 6 months and a dismal 5-year survival rate of 3-5%. These statistics highlight an urgent need for novel chemopreventive and therapeutic strategies for this malignancy. Metformin and aspirin have been explored as two emerging cancer chemoprevention agents for different types of cancers, including pancreatic cancer. Here, we review the effects of both metformin and aspirin on pancreatic tumorigenesis and their potential actions in pancreatic cancer. Special attention is paid to their effects on the important signaling pathways of pancreatic cancer development as well as possible mechanisms for synergy between these two agents. For metformin, the most important mechanism may involve the inhibition of mTOR signaling via AMPK-dependent and -independent pathways. For aspirin, the major mechanism is the anti-inflammatory action through the inhibition of Cox-1/Cox-2 and modulation of the NFκB or STAT3 pathway. Additionally, aspirin may activate AMPK, and both agents may affect Notch, Wnt/β and other signaling pathways. The combination of metformin and aspirin will provide additive and possibly synergistic effects for the prevention and treatment of pancreatic cancer.

PMID:24520038   [PubMed – as supplied by publisher]