Experimental and Molecular Medicine

Korean Society for Biochemistry and Molecular Biongy (생화학분자생물학회)
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Aldehyde dehydrogenase is used by cancer cells for energy metabolism

  • Kang, Joon Hee (Cancer Cell and Molecular Biology Branch, National Cancer Center, Research Institute) ;
  • Lee, Seon-Hyeong (Cancer Cell and Molecular Biology Branch, National Cancer Center, Research Institute) ;
  • Hong, Dongwan (Cancer Immunology Branch, National Cancer Center, Research Institute) ;
  • Lee, Jae-Seon (Cancer Cell and Molecular Biology Branch, National Cancer Center, Research Institute) ;
  • Ahn, Hee-Sung (Center for Theragnosis, Biomedical Research Institute, Korea Institute of Science and Technology) ;
  • Ahn, Ju-Hyun (Department of Biochemistry and Molecular Biology, Ajou University School of Medicine, Genomic Instability Research Center) ;
  • Seong, Tae Wha (Cancer Cell and Molecular Biology Branch, National Cancer Center, Research Institute) ;
  • Lee, Chang-Hun (Cancer Cell and Molecular Biology Branch, National Cancer Center, Research Institute) ;
  • Jang, Hyonchol (Cancer Cell and Molecular Biology Branch, National Cancer Center, Research Institute) ;
  • Hong, Kyeong Man (Omics Core Laboratory, National Cancer Center, Research Institute) ;
  • Lee, Cheolju (Center for Theragnosis, Biomedical Research Institute, Korea Institute of Science and Technology) ;
  • Lee, Jae-Ho (Department of Biochemistry and Molecular Biology, Ajou University School of Medicine, Genomic Instability Research Center) ;
  • Kim, Soo-Youl (Cancer Cell and Molecular Biology Branch, National Cancer Center, Research Institute)
  • Received : 2016.04.20
  • Accepted : 2016.06.29
  • Published : 2016.11.30
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Abstract

We found that non-small-cell lung cancer (NSCLC) cells express high levels of multiple aldehyde dehydrogenase (ALDH) isoforms via an informatics analysis of metabolic enzymes in NSCLC and immunohistochemical staining of NSCLC clinical tumor samples. Using a multiple reaction-monitoring mass spectrometry analysis, we found that multiple ALDH isozymes were generally abundant in NSCLC cells compared with their levels in normal IMR-90 human lung cells. As a result of the catalytic reaction mediated by ALDH, NADH is produced as a by-product from the conversion of aldehyde to carboxylic acid. We hypothesized that the NADH produced by ALDH may be a reliable energy source for ATP production in NSCLC. This study revealed that NADH production by ALDH contributes significantly to ATP production in NSCLC. Furthermore, gossypol, a pan-ALDH inhibitor, markedly reduced the level of ATP. Gossypol combined with phenformin synergistically reduced the ATP levels, which efficiently induced cell death following cell cycle arrest.

Keywords

Acknowledgement

Supported by : National Cancer Center of Korea, NRF

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