Targeting the AMP-Activated Protein Kinase for Cancer Prevention and Therapy

Abstract

Despite the advances in biomedical research and clinical applications, cancer remains a leading cause of death worldwide. Given the limitations of conventional chemotherapeutics, including serious toxicities and reduced quality of life for patients, the development of safe and efficacious alternatives with known mechanism of action is much needed. Prevention of cancer through dietary intervention may hold promise and has been investigated extensively in the recent years. AMP-activated protein kinase (AMPK) is an energy sensor that plays a key role in the regulation of protein and lipid metabolism in response to changes in fuel availability. When activated, AMPK promotes energy-producing catabolic pathways while inhibiting anabolic pathways, such as cell growth and proliferation – thereby antagonizing carcinogenesis. Other anti-cancer effects of AMPK may include promoting autophagy and DNA repair upon UVB damage. In the last decade, interest in AMPK has grown extensively as it emerged as an attractive target molecule for cancer prevention and treatment. Among the latest developments is the activation of AMPK by naturally occurring dietary constituents and plant products – termed phytochemicals. Owing to their efficacy and safety, phytochemicals are considered as an alternative to the conventional harmful chemotherapy. The rising popularity of using phytochemicals for cancer prevention and therapy is supported by a substantial progress in identifying the molecular pathways involved, including AMPK. In this article, we review the recent progress in this budding field that suggests AMPK as a new molecular target in the prevention and treatment of cancer by phytochemicals.

Gas1 Inhibits Metastatic and Metabolic Phenotypes in Colorectal Carcinoma

“…The results of this study revealed that Gas1 inhibited EMT and Warburg effect through the AMPK/mTOR/P70S6K pathway. Based on the decisive role of AMPK/mTOR/P70S6K on cell-cycle and nutrient sensing (34)(35)(36), in combination with our observation of the inhibitory role of Gas1 in proliferation, we speculated that Gas1 was connected to the activation of AMPK/mTOR/S6K axis and had an impact on the total and active states of AMPK/mTOR/S6K signaling pathway.…”

Knockdown of MAGEA6 Activates AMP-Activated Protein Kinase (AMPK) Signaling to Inhibit Human Renal Cell Carcinoma Cells

“…Recent studies have also proposed AMPK as a key tumor suppressor protein [12-14]. Activated AMPK exerts anti-cancer functions via different mechanisms, including mTOR complex 1 (mTORC1) inhibition [15], autophagy induction [16], p53 activation [17], as well as degradation of several key oncogenic proteins [18, 19]. AMPK can also modulate epithelial-to-messenchymal transition (EMT) via regulating Akt-MDM2-Foxo3 signaling [20].…”

Condensed catechins and their potential health-benefits

“…AMPK, a serine-threonine kinase protein complex that plays a role in the regulation of energy balance in diverse organs, is closely associated with the prevention of lifestyle-related diseases such as obesity, diabetes, and metabolic syndrome (Steinberg and Kemp, 2009). The activation of AMPK requires the phosphorylation of Thr-172 at the loops of α1 and α2 subunits by the activation of upstream kinases, including liver kinase B1 (LKB1), Ca 2 þ /calmodulindependent protein kinase kinase (CaMKK), or transforming growth factor-ß-activated kinase (TAK-1) (Hardie, 2008;Kim and He, 2013). Within our limited findings, it still remains unclear which up-stream signalling mechanism(s) are involved in the AMPK activation by theaflavins in Caco-2 cells, although the CaMKK/AMPK pathway was able to be excluded .…”