title: [D-Arg1,D-Trp5,7,9,Leu11]substance P: a novel potent inhibitor of signal transduction and growth in vitro and in vivo in small cell lung cancer cells.
abstract: [D-Arg1,D-Trp5,7,9,Leu11]Substance P (SP) was identified out of a panel of novel SP analogues as the most potent inhibitor of small cell lung cancer (SCLC) cell growth. This analogue inhibited proliferation of H-510 and H-69 SCLC cells in liquid culture and in semisolid media (IC50, 5 microM). Colony formation stimulated by multiple neuropeptides, including vasopressin and bradykinin, was also blocked by [D-Arg1,D-Trp5,7,9,Leu11]SP. This new SP analogue inhibited vasopressin- or bradykinin-induced Ca2+ mobilization and mitogen-activated protein kinase activation. Administration of [D-Arg1,D-Trp5,7,9,Leu11]SP inhibited the growth of an H-69 xenograft in nude mice. Our results support the hypothesis that SP analogue broad-spectrum neuropeptide antagonists could be of therapeutic value in SCLC.
authors.affiliation: Imperial Cancer Research Fund, London, United Kingdom.
authors.forename: M J
authors.initials: MJ
authors.lastname: Seckl
authors.forename: T
authors.initials: T
authors.lastname: Higgins
authors.forename: F
authors.initials: F
authors.lastname: Widmer
authors.forename: E
authors.initials: E
authors.lastname: Rozengurt
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry / Q000627:therapeutic use*; D002118:Calcium / Q000378:metabolism; D018288:Carcinoma, Small Cell / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D002455:Cell Division / Q000187:drug effects; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008819:Mice, Nude; D013373:Substance P / Q000031:analogs & derivatives* / Q000737:chemistry / Q000627:therapeutic use; D014407:Tumor Cells, Cultured; D014410:Tumor Stem Cell Assay
chemical_list: D000970:Antineoplastic Agents; C102471:substance P, Arg(1)-Trp(5,7,9)-Leu(11)-; D013373:Substance P; D002118:Calcium