scholarly journals Reactive oxygen species dependent phosphorylation of the liver kinase B1/AMP activated protein kinase/ acetyl-CoA carboxylase signaling is critically involved in apoptotic effect of lambertianic acid in hepatocellular carcinoma cells

Oncotarget ◽  
2017 ◽  
Vol 8 (41) ◽  
pp. 70116-70129 ◽  
Author(s):  
Arong Jeong ◽  
Ju-Ha Kim ◽  
Hyo-Jung Lee ◽  
Sung-Hoon Kim
Keyword(s):  
Hepatocellular Carcinoma ◽  
Reactive Oxygen Species ◽  
Protein Kinase ◽  
Carcinoma Cells ◽  
Oxygen Species ◽  
Acetyl Coa Carboxylase ◽  
Apoptotic Effect ◽  
Liver Kinase B1 ◽  
Lambertianic Acid ◽  
Amp Activated Protein Kinase

scholarly journals Differential regulation of AMP-activated protein kinase in healthy and cancer cells explains why V-ATPase inhibition selectively kills cancer cells

2019 ◽  
Vol 294 (46) ◽  
pp. 17239-17248
Author(s):  
Karin Bartel ◽  
Rolf Müller ◽  
Karin von Schwarzenberg
Keyword(s):  
Reactive Oxygen Species ◽  
Protein Kinase ◽  
Cancer Cells ◽  
Reactive Oxygen Species Production ◽  
Differential Regulation ◽  
Oxygen Species ◽  
Atpase Inhibitors ◽  
Species Production ◽  
Amp Activated Protein Kinase ◽  
Atpase Inhibition

The cellular energy sensor AMP-activated protein kinase (AMPK) is a metabolic hub regulating various pathways involved in tumor metabolism. Here we report that vacuolar H+-ATPase (V-ATPase) inhibition differentially affects regulation of AMPK in tumor and nontumor cells and that this differential regulation contributes to the selectivity of V-ATPase inhibitors for tumor cells. In nonmalignant cells, the V-ATPase inhibitor archazolid increased phosphorylation and lysosomal localization of AMPK. We noted that AMPK localization has a prosurvival role, as AMPK silencing decreased cellular growth rates. In contrast, in cancer cells, we found that AMPK is constitutively active and that archazolid does not affect its phosphorylation and localization. Moreover, V-ATPase–independent AMPK induction in tumor cells protected them from archazolid-induced cytotoxicity, further underlining the role of AMPK as a prosurvival mediator. These observations indicate that AMPK regulation is uncoupled from V-ATPase activity in cancer cells and that this makes them more susceptible to cell death induction by V-ATPase inhibitors. In both tumor and healthy cells, V-ATPase inhibition induced a distinct metabolic regulatory cascade downstream of AMPK, affecting ATP and NADPH levels, glucose uptake, and reactive oxygen species production. We could attribute the prosurvival effects to AMPK's ability to maintain redox homeostasis by inhibiting reactive oxygen species production and maintaining NADPH levels. In summary, the results of our work indicate that V-ATPase inhibition has differential effects on AMPK-mediated metabolic regulation in cancer and healthy cells and explain the tumor-specific cytotoxicity of V-ATPase inhibition.

scholarly journals Arecoline inhibits the growth of 3T3-L1 preadipocytes via AMP-activated protein kinase and reactive oxygen species pathways

PLoS ONE ◽  
2018 ◽  
Vol 13 (7) ◽  
pp. e0200508
Author(s):  
Zi-Han Tian ◽  
Jueng-Tsueng Weng ◽  
Li-Jane Shih ◽  
An-Ci Siao ◽  
Tsai-Yun Chan ◽  
...  
Keyword(s):  
Reactive Oxygen Species ◽  
Protein Kinase ◽  
Reactive Oxygen ◽  
Oxygen Species ◽  
Amp Activated Protein Kinase
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