Institute of Molecular and Cellular Biology, Department of Life Science, National Taiwan University, Taipei, Taiwan.
PLoS One. 2013 Aug 21;8(8):e70642. doi: 10.1371/journal.pone.0070642. eCollection 2013.
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.
ATP 合酶存在于几种类型的癌细胞的质膜上。桔青霉素是一种 ATP 合酶抑制剂，它选择性地抑制肺癌的增殖和生长，而不影响正常细胞。然而，在体内靶向异位 ATP 合酶的全局影响尚未得到很好的定义。在这项研究中，我们使用相对和绝对定量同位素标记（iTRAQ）进行了定量蛋白质组学分析，并在肺癌异种移植模型中提供了对桔青霉素复杂调控的全面了解。由于定量的高重现性，我们获得了 2659 种蛋白质的定量蛋白质组学图谱。通过相对丰度选择的 141 个差异表达蛋白的生物信息学分析表明，桔青霉素诱导肺癌中葡萄糖代谢相关酶表达的改变。参与糖异生和葡萄糖储存的酶的上调表明，桔青霉素可能减少用于大分子合成的糖酵解中间产物，并抑制细胞增殖。通过综合蛋白质组学，研究结果确定了有助于解释桔青霉素在肺癌中的抗肿瘤作用的代谢方面，这可能有助于更好地理解癌症治疗中代谢与肿瘤发生之间的联系。
