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Anti-Cancer Agents in Medicinal Chemistry

Editor-in-Chief

ISSN (Print): 1871-5206
ISSN (Online): 1875-5992

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

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

Volume 15 , Issue 5 , 2015

Page: [657 - 671] Pages: 15

DOI: 10.2174/1871520615666141216145417

Price: $65

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.

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

Graphical Abstract

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