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 00:00:00 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), Vol. 85:6; ISSN 0027-8424
• Country of Publication: United States
• Language: English

Related Subjects

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