title: Lessons from Nature: Sources and Strategies for Developing AMPK Activators for Cancer Chemotherapeutics.
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.
authors.forename: Richard T
authors.initials: RT
authors.lastname: Arkwright
authors.forename: Rahul
authors.initials: R
authors.lastname: Deshmukh
authors.forename: Nikhil
authors.initials: N
authors.lastname: Adapa
authors.forename: Ryan
authors.initials: R
authors.lastname: Stevens
authors.forename: Emily
authors.initials: E
authors.lastname: Zonder
authors.forename: Zhongyu
authors.initials: Z
authors.lastname: Zhang
authors.forename: Pershang
authors.initials: P
authors.lastname: Farshi
authors.forename: Reda Saber Ibrahim
authors.initials: RS
authors.lastname: Ahmed
authors.forename: Hossny Awad
authors.initials: HA
authors.lastname: El-Banna
authors.forename: Tak-Hang
authors.initials: TH
authors.lastname: Chan
authors.affiliation: Barbara Ann Karmanos Cancer Institute and Department of Oncology, School of Medicine, Wayne State University, 540.1 HWCRC, 4100 John R Road, Detroit, MI 48201- 2013. doup@karmanos.org.
authors.forename: Q Ping
authors.initials: QP
authors.lastname: Dou
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000378:metabolism*; D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology*; D049109:Cell Proliferation / Q000187:drug effects; D020536:Enzyme Activators / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy* / Q000201:enzymology / Q000473:pathology
chemical_list: D000970:Antineoplastic Agents; D020536:Enzyme Activators; D055372:AMP-Activated Protein Kinases