TRAP1 Inhibition Increases Glutamine Synthetase Activity in Glutamine Auxotrophic Non-small Cell Lung Cancer Cells

Cancer cells are distinct in terms of glutamine dependence. Here we investigated the different susceptibility of glutamine-independent and glutamine-dependent non-small cell lung cancer (NSCLC) to treatment with tumor necrosis factor receptor-associated protein 1 (TRAP1) inhibitor gamitrinib-triphen...

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Bibliographic Details
Published in:Anticancer research 2018-04, Vol.38 (4), p.2187-2193
Main Authors: Vo, Vu T A, Choi, Jong-Whan, Phan, Ai N H, Hua, Tuyen N M, Kim, Min-Kyu, Kang, Byoung Heon, Jung, Soon-Hee, Yong, Suk-Joong, Jeong, Yangsik
Format: Article
Language:English
Subjects:
AMP
AMP-activated protein kinase
Cancer
Cell death
Colorimetry
Dependence
Deprivation
Energy shortages
Gene expression
Glutamate-ammonia ligase
Glutamine
Kinases
Lung cancer
Metabolism
Non-small cell lung carcinoma
Polymerase chain reaction
Proteins
Therapeutic applications
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Summary:Cancer cells are distinct in terms of glutamine dependence. Here we investigated the different susceptibility of glutamine-independent and glutamine-dependent non-small cell lung cancer (NSCLC) to treatment with tumor necrosis factor receptor-associated protein 1 (TRAP1) inhibitor gamitrinib-triphenylphosphonium (G-TPP). Cell viability and proliferation under glutamine deprivation and G-TPP treatment were determined by the MTT and colony-formation assays. Protein and mRNA expression were determined by western blot and quantitative polymerase chain reaction. Colorimetric-based assay was performed to check for glutamine synthetase (GS) activity. NSCLC cells showed diverse adaptation under glutamine-depleted condition and were categorized into glutamine-independent and glutamine-dependent cells. Treatment with G-TPP particularly increased GS activity and induced cell death due to energy shortage indicated by phosphorylated AMP-activated protein kinase (AMPK) in glutamine-dependent cells. This finding provides better understanding of TRAP1-mediated glutamine metabolism through GS activity, and evidence that TRAP1 could be a promising therapeutic target for glutamine-addicted cancer.
ISSN:0250-7005
1791-7530
DOI:10.21873/anticanres.12460