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Lessons from Nature: Sources and Strategies for Developing AMPK Activators for
Cancer Chemotherapeutics
#MMPMID25511514
Arkwright RT
; Deshmukh R
; Adapa N
; Stevens R
; Zonder E
; Zhang Z
; Farshi P
; Ahmed RS
; El-Banna HA
; Chan TH
; Dou QP
Anticancer Agents Med Chem
2015[]; 15
(5
): 657-71
PMID25511514
show ga
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.
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