title: Quantitative proteomic analysis of human lung tumor xenografts treated with the ectopic ATP synthase inhibitor citreoviridin.
abstract: ATP synthase is present on the plasma membrane of several types of cancer cells. Citreoviridin, an ATP synthase inhibitor, selectively suppresses the proliferation and growth of lung cancer without affecting normal cells. However, the global effects of targeting ectopic ATP synthase in vivo have not been well defined. In this study, we performed quantitative proteomic analysis using isobaric tags for relative and absolute quantitation (iTRAQ) and provided a comprehensive insight into the complicated regulation by citreoviridin in a lung cancer xenograft model. With high reproducibility of the quantitation, we obtained quantitative proteomic profiling with 2,659 proteins identified. Bioinformatics analysis of the 141 differentially expressed proteins selected by their relative abundance revealed that citreoviridin induces alterations in the expression of glucose metabolism-related enzymes in lung cancer. The up-regulation of enzymes involved in gluconeogenesis and storage of glucose indicated that citreoviridin may reduce the glycolytic intermediates for macromolecule synthesis and inhibit cell proliferation. Using comprehensive proteomics, the results identify metabolic aspects that help explain the antitumorigenic effect of citreoviridin in lung cancer, which may lead to a better understanding of the links between metabolism and tumorigenesis in cancer therapy.
authors.affiliation: Institute of Molecular and Cellular Biology, Department of Life Science, National Taiwan University, Taipei, Taiwan.
authors.forename: Yi-Hsuan
authors.initials: YH
authors.lastname: Wu
authors.forename: Chia-Wei
authors.initials: CW
authors.lastname: Hu
authors.forename: Chih-Wei
authors.initials: CW
authors.lastname: Chien
authors.forename: Yu-Ju
authors.initials: YJ
authors.lastname: Chen
authors.forename: Hsuan-Cheng
authors.initials: HC
authors.lastname: Huang
authors.forename: Hsueh-Fen
authors.initials: HF
authors.lastname: Juan
mesh_terms: D000465:Algorithms; D000818:Animals; D001313:Aurovertins / Q000737:chemistry / Q000494:pharmacology*; D002412:Cations; D002462:Cell Membrane / Q000378:metabolism; D049109:Cell Proliferation; D002853:Chromatography, Liquid; D019295:Computational Biology; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000494:pharmacology*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D005943:Gluconeogenesis; D005947:Glucose / Q000378:metabolism; D006019:Glycolysis; D006801:Humans; D019394:Ki-67 Antigen / Q000378:metabolism; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000378:metabolism*; D051379:Mice; D008819:Mice, Nude; D025261:Mitochondrial Proton-Translocating ATPases / Q000037:antagonists & inhibitors*; D020543:Proteome; D053719:Tandem Mass Spectrometry; D023041:Xenograft Model Antitumor Assays
chemical_list: D001313:Aurovertins; D002412:Cations; D004791:Enzyme Inhibitors; D019394:Ki-67 Antigen; D020543:Proteome; D025261:Mitochondrial Proton-Translocating ATPases; D005947:Glucose; C014416:citreoviridin