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

被引:12
作者
Vo, Vu T. A. [1 ,2 ]
Choi, Jong-Whan [1 ]
Phan, Ai N. H. [1 ,2 ]
Hua, Tuyen N. M. [1 ,2 ]
Kim, Min-Kyu [1 ,2 ]
Kang, Byoung Heon [5 ]
Jung, Soon-Hee [3 ]
Yong, Suk-Joong [4 ]
Jeong, Yangsik [1 ,2 ]
机构
[1] Yonsei Univ, Wonju Coll Med, Dept Biochem, 20 Ilsan Ro, Wonju 26426, Gangwon Do, South Korea
[2] Yonsei Univ, Wonju Coll Med, Dept Global Med Sci, Med Res Ctr,Inst Lifestyle Med, Wonju, South Korea
[3] Yonsei Univ, Wonju Coll Med, Dept Pathol, Wonju, South Korea
[4] Yonsei Univ, Wonju Coll Med, Dept Internal Med, 20 Ilsan Ro, Wonju 26426, Gangwon Do, South Korea
[5] Ulsan Natl Inst Sci & Technol, Dept Biol Sci, Ulsan, South Korea
基金
新加坡国家研究基金会;
关键词
Glutamine metabolism; TRAP1; gamitrinib-triphenylphosphonium; glutamine synthetase; lung cancer; MITOCHONDRIAL HSP90; METABOLISM; THERAPY; EXPRESSION; NETWORKS; PROTEIN; GROWTH; NSCLC;
D O I
10.21873/anticanres.12460
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Background/Aim: 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). Materials and Methods: 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. Results: 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. Conclusion: 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.
引用
收藏
页码:2187 / 2193
页数:7
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