title: TBMS1 exerts its cytotoxicity in NCI-H460 lung cancer cells through nucleolar stress-induced p53/MDM2-dependent mechanism, a quantitative proteomics study.
abstract: Tubeimoside-1 (TBMS1) exerts its anticancer effects by inducing G2/M arrest and apoptosis of cancer cells. However, the precise molecular mechanism of its anti-tumor effects has not been fully elucidated, especially the signaling pathways involved in the early stage of TBMS1 stimulation. In this study, we employed stable isotope labeling by amino acids in cell culture (SILAC)-based quantitative proteomics approach and identified 439 proteins that exhibit significant differential expressions in NCI-H460 lung cancer cells upon exposure to TBMS1. Gene ontology and network analysis using DAVID and STRING on-line tools revealed that several nucleolar stress (ribosomal biogenesis) response proteins were differentially regulated by TBMS1. Functional validation demonstrated that TBMS1-induced NCI-H460 cell cytotoxicity involved nucleolar stress-induced p53/murine double minute clone 2 (MDM2), mTOR, and NF-κB signaling pathways.
authors.affiliation: School of Pharmaceutical Sciences, Xiamen University, Xiamen, Fujian, PR China.
authors.forename: Yingying
authors.initials: Y
authors.lastname: Lin
authors.affiliation: School of Pharmaceutical Sciences, Xiamen University, Xiamen, Fujian, PR China.
authors.forename: Guobin
authors.initials: G
authors.lastname: Xie
authors.affiliation: School of Pharmaceutical Sciences, Xiamen University, Xiamen, Fujian, PR China.
authors.forename: Ji
authors.initials: J
authors.lastname: Xia
authors.affiliation: School of Pharmaceutical Sciences, Xiamen University, Xiamen, Fujian, PR China.
authors.forename: Dan
authors.initials: D
authors.lastname: Su
authors.affiliation: School of Pharmaceutical Sciences, Xiamen University, Xiamen, Fujian, PR China.
authors.forename: Jie
authors.initials: J
authors.lastname: Liu
authors.affiliation: School of Pharmaceutical Sciences, Xiamen University, Xiamen, Fujian, PR China. Electronic address: jiangfq@xmu.edu.cn.
authors.forename: Fuquan
authors.initials: F
authors.lastname: Jiang
authors.affiliation: School of Pharmaceutical Sciences, Xiamen University, Xiamen, Fujian, PR China. Electronic address: xuyang@xmu.edu.cn.
authors.forename: Yang
authors.initials: Y
authors.lastname: Xu
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D059447:Cell Cycle Checkpoints / Q000187:drug effects; D045744:Cell Line, Tumor; D002466:Cell Nucleolus / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D051379:Mice; D016328:NF-kappa B / Q000235:genetics; D040901:Proteomics; D051736:Proto-Oncogene Proteins c-mdm2 / Q000235:genetics*; D012269:Ribosomal Proteins / Q000096:biosynthesis; D012503:Saponins / Q000008:administration & dosage*; D015398:Signal Transduction / Q000187:drug effects; D058570:TOR Serine-Threonine Kinases / Q000235:genetics; D014315:Triterpenes / Q000008:administration & dosage*; D016159:Tumor Suppressor Protein p53 / Q000235:genetics*
chemical_list: D016328:NF-kappa B; D012269:Ribosomal Proteins; D012503:Saponins; C495901:TP53 protein, human; D014315:Triterpenes; D016159:Tumor Suppressor Protein p53; C051084:tubeimoside I; C497206:MDM2 protein, human; D051736:Proto-Oncogene Proteins c-mdm2; C546842:MTOR protein, human; D058570:TOR Serine-Threonine Kinases
keywords: Nucleolar stress; Quantitative proteomics; SILAC; TBMS1; p53