Substance P, a potent bombesin antagonist in murine Swiss 3T3 cells, inhibits the growth of human small cell lung cancer cells in vitro

Journal Article · Tue Mar 01 04:00:00 EST 1988 · Proceedings of the National Academy of Sciences of the United States of America; (USA)

DOI:https://doi.org/10.1073/pnas.85.6.1859· OSTI ID:6897569

Woll, P J; Rozengurt, E ^[1]

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1. Imperial Cancer Research Fund, London (England)

In the search for a more potent bombesin antagonist, the authors found (D-Arg{sup 1},D-Phe{sup 5},D-Trp{sup 7,9},Leu{sup 11})substance P to be effective in mouse fibroblasts and to inhibit the growth of small cell lung cancer, a tumor that secretes bombesin-like peptides that may act as autocrine growth factors. In murine Swiss 3T3 cells, substance P proved to be a bombesin antagonist as judged by the following criteria: (i) inhibition of DNA synthesis induced by gastrin-releasing peptide and other bombesin-like peptides; (ii) inhibition of {sup 125}I-labeled gastrin-releasing peptide binding to the bombesin/gastrin-releasing peptide receptor; (iii) reduction in cross-linking of the M{sub r} 75,000-85,000 protein putatively a component of the bombesin/gastrin-releasing peptide receptor; (iv) blocking of early cellular events that precede mitogenesis-calcium mobilization and inhibition of epidermal growth factor binding. Substance P also inhibits mitogenesis induced by vasopressin but not that induced by a variety of other mitogens. Both antagonists reversibly inhibited the growth of small cell lung cancer in vitro in a concentration-dependent manner. Peptide antagonists could, therefore, have far-reaching therapeutic implications.

• OSTI ID: 6897569
• Journal Information: Proceedings of the National Academy of Sciences of the United States of America; (USA), Journal Name: Proceedings of the National Academy of Sciences of the United States of America; (USA) Vol. 85:6; ISSN 0027-8424; ISSN PNASA
• Country of Publication: United States
• Language: English

Related Subjects

550201* -- Biochemistry-- Tracer Techniques
59 BASIC BIOLOGICAL SCIENCES
ANIMAL CELLS
ANIMALS
BETA DECAY RADIOISOTOPES
BIOCHEMISTRY
CHEMICAL REACTIONS
CHEMISTRY
CONNECTIVE TISSUE CELLS
CROSS-LINKING
DAYS LIVING RADIOISOTOPES
DNA REPLICATION
ELECTRON CAPTURE RADIOISOTOPES
FIBROBLASTS
INHIBITION
INTERMEDIATE MASS NUCLEI
IODINE 125
IODINE ISOTOPES
ISOTOPES
LABELLED COMPOUNDS
MAMMALS
MEMBRANE PROTEINS
MICE
NUCLEI
NUCLEIC ACID REPLICATION
ODD-EVEN NUCLEI
ORGANIC COMPOUNDS
PEPTIDES
POLYMERIZATION
PROTEINS
RADIOISOTOPES
RECEPTORS
RODENTS
SOMATIC CELLS
TUMOR CELLS
VERTEBRATES