[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.
[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.
Seckl
M J
MJ
Imperial Cancer Research Fund, London, United Kingdom.
Higgins
T
T
Widmer
F
F
Rozengurt
E
E
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
D000970:Antineoplastic Agents; C102471:substance P, Arg(1)-Trp(5,7,9)-Leu(11)-; D013373:Substance P; D002118:Calcium