title: Camptothecin promotes the production of nitric oxide that triggers subsequent S-nitrosoproteome-mediated signaling cascades in endothelial cells.
abstract: Camptothecin (CPT) has been used for colorectal cancer therapy. At low concentration of 10-9M, CPT modulates endothelial nitric oxide production following the phosphorylation of LKB1 Ser431, AMPK-α Thr172, eNOS Ser633 and Ser1177. Elevated nitric oxide (NO) was observed by FA-OMe fluorescent probe. 726 S-nitrosoproteins were identified by iTRAQ quantitative proteomics. IPA analysis indicated that ERK/MAPK was closely linked in the signaling network. Further studies showed that CPT phosphorylated p38 MAPK Thr180/Tyr182 and dephosphorylated Tau Ser199/202. CPT also suppressed the TNF-α-induced expression of the inflammasome and cyclooxygenase 2. All this suggests that in addition to the original character of CPT in attenuating the binding of topoisomerase I and DNA in cancer cells, the role of CPT in triggering NO production and the subsequent S-nitrosylated signaling including anti-inflammatory effects in endothelial cells are proposed here. CPT, therefore, provides a potential application addition in preventing vascular disorders.
authors.affiliation: Department of Biomedical Science and Environmental Biology, College of Life Science, Kaohsiung Medical University, Kaohsiung 80708, Taiwan; Center for Biomarkers and Biotech Drugs, Kaohsiung Medical University, Kaohsiung, 80708, Taiwan; Department of Biological Sciences, National Sun Yat-sen University, Kaohsiung 80424, Taiwan. Electronic address: huangpin2@kmu.edu.tw.
authors.forename: Bin
authors.initials: B
authors.lastname: Huang
authors.affiliation: Department of Medicine, MacKay Medical College, New Taipei City 25245, Taiwan; Department of Anesthesiology, MacKay Memorial Hospital, Taipei 10449, Taiwan; MacKay Junior College of Medicine, Nursing, and Management, Taipei 11260, Taiwan.
authors.forename: Jen-Kun
authors.initials: JK
authors.lastname: Cheng
authors.affiliation: Department of Pediatrics, E-Da Hospital, Kaohsiung, 82445, Taiwan; School of Medicine, College of Medicine, I-Shou University, Kaohsiung 84001, Taiwan.
authors.forename: Chien-Yi
authors.initials: CY
authors.lastname: Wu
authors.affiliation: School of Dentistry, College of Dental Medicine, Kaohsiung Medical University, Kaohsiung 80708, Taiwan.
authors.forename: Ping-Ho
authors.initials: PH
authors.lastname: Chen
authors.affiliation: Department of Biomedical Science and Environmental Biology, College of Life Science, Kaohsiung Medical University, Kaohsiung 80708, Taiwan.
authors.forename: Po-Shu
authors.initials: PS
authors.lastname: Tu
authors.affiliation: Department of Biomedical Science and Environmental Biology, College of Life Science, Kaohsiung Medical University, Kaohsiung 80708, Taiwan. Electronic address: m805004@kmu.edu.tw.
authors.forename: Yaw-Syan
authors.initials: YS
authors.lastname: Fu
authors.affiliation: Division of Nephrology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University, College of Medicine, Kaohsiung 83301, Taiwan; Center for General Education, Cheng Shiu University, Kaohsiung 83347, Taiwan. Electronic address: vjf3@cgmh.org.tw.
authors.forename: Chien-Hsing
authors.initials: CH
authors.lastname: Wu
mesh_terms: D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D002166:Camptothecin / Q000494:pharmacology*; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D061307:Human Umbilical Vein Endothelial Cells / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D058847:Inflammasomes / Q000378:metabolism; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism*; D052250:Nitric Oxide Synthase Type III / Q000378:metabolism; D015538:Nitrosation; D010766:Phosphorylation; D060066:Protein Interaction Maps; D011499:Protein Processing, Post-Translational; D020543:Proteome / Q000378:metabolism*; D040901:Proteomics / Q000379:methods; D015398:Signal Transduction / Q000187:drug effects*; D013997:Time Factors; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism; D016875:tau Proteins / Q000378:metabolism
chemical_list: D000893:Anti-Inflammatory Agents; D058847:Inflammasomes; C054369:MAPT protein, human; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; C453881:NLRP3 protein, human; D020543:Proteome; D016875:tau Proteins; D009569:Nitric Oxide; C496314:NOS3 protein, human; D052250:Nitric Oxide Synthase Type III; D048051:p38 Mitogen-Activated Protein Kinases; D002166:Camptothecin
keywords: Acetonitrile (PubChem CID: 6342); Ascorbic acid (PubChem CID: 54670067); Biotin-HPDP (PubChem CID: 15949894); CHAPS (PubChem CID: 107670); Camptothecin; Camptothecin (PubChem CID: 24360); DAPI (PubChem CID: 2954); DMSO (PubChem CID: 679); Endothelial cells; Formic acid (PubChem CID: 284); Inflammation; MMTS (PubChem CID: 18064); Neocuproine (PubChem CID: 65237); Nitric oxide; S-nitrosoproteome; eNOS