title: Aldehyde dehydrogenase is used by cancer cells for energy metabolism.
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.
authors.affiliation: Cancer Cell and Molecular Biology Branch, National Cancer Center, Research Institute, Goyang, Gyeonggi-do, Republic of Korea.
authors.forename: Joon Hee
authors.initials: JH
authors.lastname: Kang
authors.affiliation: Cancer Cell and Molecular Biology Branch, National Cancer Center, Research Institute, Goyang, Gyeonggi-do, Republic of Korea.
authors.forename: Seon-Hyeong
authors.initials: SH
authors.lastname: Lee
authors.affiliation: Cancer Immunology Branch, National Cancer Center, Research Institute, Goyang, Gyeonggi-do, Republic of Korea.
authors.forename: Dongwan
authors.identifier: 0000-0002-7816-1299
authors.initials: D
authors.lastname: Hong
authors.affiliation: Cancer Cell and Molecular Biology Branch, National Cancer Center, Research Institute, Goyang, Gyeonggi-do, Republic of Korea.
authors.forename: Jae-Seon
authors.initials: JS
authors.lastname: Lee
authors.affiliation: Center for Theragnosis, Biomedical Research Institute, Korea Institute of Science and Technology, Seoul, Republic of Korea.|Department of Biological Chemistry, University of Science and Technology, Daejeon, Republic of Korea.
authors.forename: Hee-Sung
authors.initials: HS
authors.lastname: Ahn
authors.affiliation: Department of Biochemistry and Molecular Biology, Ajou University School of Medicine, Genomic Instability Research Center, Suwon, Korea.|Department of Biomedical Sciences, The Graduate School, Ajou University, Suwon, Korea.
authors.forename: Ju-Hyun
authors.initials: JH
authors.lastname: Ahn
authors.affiliation: Cancer Cell and Molecular Biology Branch, National Cancer Center, Research Institute, Goyang, Gyeonggi-do, Republic of Korea.
authors.forename: Tae Wha
authors.initials: TW
authors.lastname: Seong
authors.affiliation: Cancer Cell and Molecular Biology Branch, National Cancer Center, Research Institute, Goyang, Gyeonggi-do, Republic of Korea.
authors.forename: Chang-Hun
authors.initials: CH
authors.lastname: Lee
authors.affiliation: Cancer Cell and Molecular Biology Branch, National Cancer Center, Research Institute, Goyang, Gyeonggi-do, Republic of Korea.
authors.forename: Hyonchol
authors.initials: H
authors.lastname: Jang
authors.affiliation: Omics Core Laboratory, National Cancer Center, Research Institute, Goyang, Republic of Korea.
authors.forename: Kyeong Man
authors.initials: KM
authors.lastname: Hong
authors.affiliation: Center for Theragnosis, Biomedical Research Institute, Korea Institute of Science and Technology, Seoul, Republic of Korea.|Department of Biological Chemistry, University of Science and Technology, Daejeon, Republic of Korea.
authors.forename: Cheolju
authors.initials: C
authors.lastname: Lee
authors.affiliation: Department of Biochemistry and Molecular Biology, Ajou University School of Medicine, Genomic Instability Research Center, Suwon, Korea.|Department of Biomedical Sciences, The Graduate School, Ajou University, Suwon, Korea.
authors.forename: Jae-Ho
authors.initials: JH
authors.lastname: Lee
authors.affiliation: Cancer Cell and Molecular Biology Branch, National Cancer Center, Research Institute, Goyang, Gyeonggi-do, Republic of Korea.
authors.forename: Soo-Youl
authors.initials: SY
authors.lastname: Kim
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D000444:Aldehyde Dehydrogenase / Q000032:analysis / Q000235:genetics / Q000378:metabolism*; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D002460:Cell Line; D045744:Cell Line, Tumor; D004734:Energy Metabolism; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008168:Lung / Q000378:metabolism / Q000473:pathology; D008175:Lung Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D009243:NAD / Q000378:metabolism; D020033:Protein Isoforms / Q000032:analysis / Q000235:genetics / Q000378:metabolism
chemical_list: D020033:Protein Isoforms; D009243:NAD; D000255:Adenosine Triphosphate; D000444:Aldehyde Dehydrogenase