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Substance P analogues function as bombesin receptor antagonists and inhibit small cell lung cancer clonal growth |
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| Authors: | Gerold Bepler Uwe Zeymer Samira Mahmoud Gary Fiskum Edmund Palaszynski Martin Rotsch James Willey Aurelia Koros Frank Cuttitta Terry W. Moody |
| Affiliation: | a Philipps University Marburg, Department of Internal Medicine Division of Hematology and Oncology, 3550, Marburg, West Germany b Department of Biochemistry, The George Washington University School of Medicine and Health Sciences, Washington, DC 20037, USA c Laboratory of Human Carcinogenesis, National Cancer Institute, Bethesda, MD 20892, USA d Department of Microbiology, Graduate School of Public Health University of Pittsburgh, Pittsburgh, PA 15261, USA e NCI-Navy Medical Oncology Branch, Division of Cancer Treatment National Cancer Institute and Naval Hospital, Bethesda, MD 20814, USA |
| Abstract: | Human small cell lung cancer (SCLC) produces and secretes BN/GRP (bombesin/gastrin releasing peptide). Because BN stimulates the growth of SCLC cells and these cells have receptors for BN-like peptides, it is important to define agents which disrupt this self-promoting autocrine growth cycle. Here, substance P analogues were evaluated as BN receptor antagonists using SCLC cell lines. (D-Arg1, D-Pro2, D-Trp7,9, Leu11) substance P [(APTTL)SP] was one of the more potent analogues tested in inhibiting BN-like peptide receptor binding with an IC50 value of 1 μM. Micromolar concentrations of (APTTL)SP antagonized BN receptor mediated elevation of cytosolic Ca2+ levels and decreased the colony formation in soft agarose. These data suggest that SP analogues function as SCLC BN receptor antagonists and may be useful in disrupting the autocrine growth function of BN-like peptides. |
| Keywords: | Small cell lung cancer Bombesin receptors Substance P analogues Cytosolic Ca2+ Clonal growth |
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