Targeting Energy Metabolic and Oncogenic Signaling Pathways in Triple-negative Breast Cancer by a Novel Adenosine Monophosphate-activated Protein Kinase (AMPK) Activator

Abstract

Background: Adenosine monophosphate-activated protein kinase (AMPK) modulates cancer cell metabolism and survival. Results: The novel compound OSU-53 directly activates AMPK, inhibits multiple metabolic and oncogenic pathways, and induces apoptosis in triple-negative breast cancer cells. Conclusion: OSU-53 acts through a broad spectrum of antitumor activities downstream of AMPK activation. Significance: OSU-53 is a potent small molecule AMPK activator with translational potential for breast cancer therapy.

25 Years of Small Molecular Weight Kinase Inhibitors: Potentials and Limitations

“…On the other hand, there are a few protein kinases that require activation rather than inhibition to fulfill their therapeutic task, like in the case of AMP-activated protein kinase and the insulin receptor for which activators have been identified (Li et al, 2001;Pender et al, 2002;Sanders et al, 2007;Lee et al, 2011;Salt and Palmer, 2012). PKC activation by exogenous compounds acting at the diaclyglycerol-binding site can have tumor-promoting or tumor-suppressive effects (Martiny- Baron and Fabbro, 2007).…”

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“…Adenosine monophosphate-activated protein kinase (AMPK) is a metabolic checkpoint in regulating energy homeostasis, and recently, AMPK activator is considered as a new therapeutic candidate in cancer therapy due to its involvement in inducing autophagy and apoptosis (Feng et al, 2014;Guo et al, 2009;Lee et al, 2011). As shown in Fig.…”

Metformin and Pancreatic Cancer Metabolism

“…Thus, metabolic enzymes involved in FA synthesis have emerged as therapeutic targets in cancer [94]. The effects of MET on energy homeostasis in normal hepatocytes and breast and colon cancer cells have been characterized by the blocked activation or expression of key lipid biosynthesis enzymes such as ACC, FAS, HMGCR and enhanced expression of regulators of mitochondrial biogenesis, peroxisome proliferator-activated receptor-gamma co-activator 1 (PGC-1) [1,74,95].…”