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.
