Quantitative proteomic analysis of human lung tumor xenografts treated with the ectopic ATP synthase inhibitor citreoviridin
Journal
PLoS ONE
Journal Volume
8
Journal Issue
8
Pages
e70642
Date Issued
2013
Author(s)
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. ? 2013 Wu et al.
SDGs
Other Subjects
citreoviridin; proton transporting adenosine triphosphate synthase; proton transporting adenosine triphosphate synthase inhibitor; unclassified drug; amino acid sequence; animal experiment; animal model; animal tissue; antineoplastic activity; article; bioinformatics; cancer inhibition; cell proliferation; controlled study; drug efficacy; enzyme activity; enzyme regulation; gluconeogenesis; glucose metabolism; glycolysis; human; human cell; limit of quantitation; lung cancer; macromolecule; mouse; nonhuman; nucleotide sequence; protein analysis; protein expression; protein function; proteomics; quantitative analysis; reproducibility; treatment response; tumor xenograft; Algorithms; Animals; Aurovertins; Cations; Cell Membrane; Cell Proliferation; Chromatography, Liquid; Computational Biology; Enzyme Inhibitors; Female; Gene Expression Regulation, Neoplastic; Gluconeogenesis; Glucose; Glycolysis; Humans; Ki-67 Antigen; Lung Neoplasms; Mice; Mice, Nude; Mitochondrial Proton-Translocating ATPases; Proteome; Tandem Mass Spectrometry; Xenograft Model Antitumor Assays
Publisher
PLoS
Type
journal article