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 , Q. Ping Dou .

Journal Name: Anti-Cancer Agents in Medicinal Chemistry

Volume 15 , Issue 5 , 2015

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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

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Article Details

VOLUME: 15
ISSUE: 5
Year: 2015
Page: [657 - 671]
Pages: 15
DOI: 10.2174/1871520615666141216145417
Price: $58

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