PMID: 7529212Jan 3, 1995Paper

New short-chain analogs of a substance-P antagonist inhibit proliferation of human small-cell lung-cancer cells in vitro and in vivo

International Journal of Cancer. Journal International Du Cancer
A OroszO Nyéki

Abstract

Human small-cell lung-cancer cells (SCLC) produce and secrete gastrin-releasing peptide (GRP), the mammalian equivalent of bombesin (BN). There is some evidence to suggest that GRP is an autocrine regulator of SCLC cell growth. In the search for potent BN antagonists, several substance-P (SP) analogs were found to inhibit the growth of SCLC cells. We found that a known short-chain SP antagonist, pHOPA-DTrp-Phe-DTrp-Leu-Leu-NH2(NY3238), inhibits the binding of 125I-Tyr4-BN on Swiss 3T3 cell line expressing BN receptors, as well as the proliferation of NCI-H69 SCLC cells. In this study we tested several analogs of NY3238 and we found that NY3521 and NY3460 are more effective in inhibition of proliferation of SCLC cells but less potent in inhibition of binding of 125I-Tyr4-BN on Swiss 3T3 cells than NY3238. Furthermore, we detected specific binding of radiolabelled NY3238 even below 1 nM on NCI-H69 cells that could have been inhibited by SP and NY3460 rather than by BN. In addition to these in vitro studies, NY3460 proved to be effective in inhibiting the growth of NCI-H69 SCLC xenografts in nude mice in vivo. These analogs of NY3238 could be promising therapeutic agents in the treatment of SCLC.

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Citations

Dec 22, 1999·Immunopharmacology·J M StewartP Bunn
Jun 6, 1997·Neuroscience Letters·P WeydtH Kettenmann
Mar 17, 2006·The International Journal of Biochemistry & Cell Biology·Antal OroszAndras Perczel
Jul 2, 2003·Amino Acids·Y L Janin
Nov 4, 2000·Expert Opinion on Investigational Drugs·F P Worden, G P Kalemkerian
Mar 24, 2005·Biopolymers·Ferenc BogárBotond Penke
Jul 2, 2005·Neuroimmunomodulation·Jill M Manske, Summer E Hanson
Sep 1, 2004·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Bieke Van Den Bossche, Christophe Van de Wiele
Jun 18, 2002·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Grace K Dy, Alex A Adjei

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