This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Woll, P. J. Articles by Rozengurt, E. Search for Related Content PubMed PubMed Citation Articles by Woll, P. J. Articles by Rozengurt, E.

A Neuropeptide Antagonist That Inhabits the Growth of Small Cell Lung Cancer in Vitro

Growth Regulation Laboratory, Imperial Cancer Research Fund, P.O. Box 123, Lincoln's Inn Fields, London WC2A 3PX, United Kingdom

In the search for novel antiproliferative agents for small cell lung cancer (SCLC), we found the neuropeptide antagonist [Arg⁶,D-Trp^7,9,MePhe⁸]substance P(6–11) to be effective in vitro. In murine Swiss 3T3 cells [Arg⁶,D-Trp^7,9,MePhe⁸]substance P(6–11) was identified as a potent inhibitor of vasopressin-stimulated DNA synthesis which also blocks [³H]vasopressin binding to specific cell-surface receptors. It was a less potent antagonist of gastrin-releasing peptide and bradykinin in these cells but did not block the effects of other mitogens.

In SCLC cell lines, [Arg⁶,D-Trp^7.9,MePhe⁸]substance P(6–11) inhibited colony-formation in soft agarose and growth in liquid culture in a dose-dependent manner. It also blocked receptor-mediated Ca²⁺ mobilization induced by vasopressin, bradykinin, cholecystokinin, galanin, gastrin-releasing peptide, and neurotensin. We suggest that broad-spectrum neuropeptide antagonists can block multiple autocrine and paracrine growth loops in SCLC and could be useful therapeutic agents.

¹ To whom requests for reprints should be addressed.

Received 2/ 9/90.

This article has been cited by other articles:

				S. Guha, G. Eibl, K. Kisfalvi, R. S. Fan, M. Burdick, H. Reber, O. J. Hines, R. Strieter, and E. Rozengurt Broad-Spectrum G Protein-Coupled Receptor Antagonist, [D-Arg1,D-Trp5,7,9,Leu11]SP: A Dual Inhibitor of Growth and Angiogenesis in Pancreatic Cancer Cancer Res., April 1, 2005; 65(7): 2738 - 2745. [Abstract] [Full Text] [PDF]

				S. Clive, D. J. Webb, A. MacLellan, A. Young, B. Byrne, L. Robson, J. F. Smyth, and D. I. Jodrell Forearm Blood Flow and Local Responses to Peptide Vasodilators: A Novel Pharmacodynamic Measure in the Phase I Trial of Antagonist G, a Neuropeptide Growth Factor Antagonist Clin. Cancer Res., October 1, 2001; 7(10): 3071 - 3078. [Abstract] [Full Text] [PDF]

				M. J. Seckl, T. Higgins, and E. Rozengurt [D-Arg1,D-Trp5,7,9,Leu11]Substance P Coordinately and Reversibly Inhibits Bombesin- and Vasopressin-induced Signal Transduction Pathways in Swiss 3T3 Cells J. Biol. Chem., November 15, 1996; 271(46): 29453 - 29460. [Abstract] [Full Text] [PDF]

				F. M. Mitchell, L. E. Heasley, N.-X. Qian, J. Zamarripa, and G. L. Johnson Differential Modulation of Bombesin-stimulated Phospholipase C[IMAGE] and Mitogen-activated Protein Kinase Activity by [ D-Arg[IMAGE], D-Phe[IMAGE], D-Trp[IMAGE],Leu[IMAGE]]Substance P J. Biol. Chem., April 14, 1995; 270(15): 8623 - 8628. [Abstract] [Full Text] [PDF]

				K Sikora Current Issues in Cancer: Genes dreams and cancer BMJ, May 7, 1994; 308(6938): 1217 - 1221. [Full Text]

				J. Sinnett-Smith, C. Santiskulvong, J. Duque, and E. Rozengurt [D-Arg1,D-Trp5,7,9,Leu11]Substance P Inhibits Bombesin-induced Mitogenic Signal Transduction Mediated by Both Gq and G12 in Swiss 3T3 Cells J. Biol. Chem., September 22, 2000; 275(39): 30644 - 30652. [Abstract] [Full Text] [PDF]