Role of AMP-activated protein kinase in cancer therapy.

Recent advances in AMP-activated protein kinase (AMPK) as a target in cancer waxed and waned over the past decade of cancer research. AMPK is a cellular energy sensor, present in almost all eukaryotic cells. An elevated AMP/ATP ratio activates the AMPK, which in turn inhibits energy-consuming processes and induces catabolic events that generate ATP to restore the energy homeostasis inside the cell. Several reports have indicated that AMPK regulates several metabolic pathways and may be a potential therapeutic target for the treatment of cancer. Cancer cells have specific metabolic changes that differ from normal cells, and AMPK prevents the deregulated processes in cancer. AMPK may also act to inhibit tumor formation through modulation of cell growth, cell proliferation, autophagy, stress responses, and cell polarity. AMPK has been shown to inhibit mammalian target of rapamycin (mTOR) through tuberous sclerosis complex 2 (TSC2) phosphorylation and phosphatase and tensin homolog (PTEN), considered as central cell growth controller signals in diseases. In response to glucose deprivation, AMPK phosphorylates and activates p53, which induces cell cycle arrest in the G1/S phase of the cell cycle. AMPK has also been reported to block cyclin-dependent kinases through phosphorylation of p27(kip1) , promoting its stabilization and allowing cells to survive metabolic stress via induction of autophagy. Additionally, AMPK induces autophagy by phosphorylation and activation of eEF-2 kinase, and prevents the formation of new proteins. AMPK activators are also used for the treatment of type II diabetes and cancer. This review focuses on AMPK activation and its possible therapeutic role in the treatment of cancer.