Lessons from Nature: Sources and Strategies for Developing AMPK Activators for Cancer Chemotherapeutics

Title:Lessons from Nature: Sources and Strategies for Developing AMPK Activators for Cancer Chemotherapeutics

Volume: 15 Issue: 5

Author(s): Richard T. Arkwright, Rahul Deshmukh, Nikhil Adapa, Ryan Stevens, Emily Zonder, Zhongyu Zhang, Pershang Farshi, Reda Saber Ibrahim Ahmed, Hossny Awad El-Banna, Tak-Hang Chan and Q. Ping Dou

Affiliation:

Keywords: AMPK, AMPK-activators, AMPK-signaling pathway, aspirin, BCA2, cancer, chemotherapy, drug discovery, metformin, natural compounds, salicylate

Abstract: Adenosine Monophosphate-Activated Protein Kinase or AMPK is a highly-conserved master-regulator of numerous cellular processes, including: Maintaining cellular-energy homeostasis, modulation of cytoskeletaldynamics, directing cell growth-rates and influencing cell-death pathways. AMPK has recently emerged as a promising molecular target in cancer therapy. In fact, AMPK deficiencies have been shown to enhance cell growth and proliferation, which is consistent with enhancement of tumorigenesis by AMPK-loss. Conversely, activation of AMPK is associated with tumor growth suppression via inhibition of the Mammalian Target of Rapamycin Complex-1 (mTORC1) or the mTOR signal pathway. The scientific communities’ recognition that AMPK-activating compounds possess an anti-neoplastic effect has contributed to a rush of discoveries and developments in AMPK-activating compounds as potential anticancer-drugs. One such example is the class of compounds known as Biguanides, which include Metformin and Phenformin. The current review will showcase natural compounds and their derivatives that activate the AMPK-complex and signaling pathway. In addition, the biology and history of AMPK-signaling and AMPK-activating compounds will be overviewed, their anticancer-roles and mechanisms-of-actions will be discussed, and potential strategies for the development of novel, selective AMPK-activators with enhanced efficacy and reduced toxicity will be proposed.

Cite this article as:

Arkwright T. Richard, Deshmukh Rahul, Adapa Nikhil, Stevens Ryan, Zonder Emily, Zhang Zhongyu, Farshi Pershang, Ahmed Saber Ibrahim Reda, El-Banna Awad Hossny, Chan Tak-Hang and Dou Ping Q., Lessons from Nature: Sources and Strategies for Developing AMPK Activators for Cancer Chemotherapeutics, Anti-Cancer Agents in Medicinal Chemistry 2015; 15 (5) . https://dx.doi.org/10.2174/1871520615666141216145417