Skip to main content
NCBI home page
British Journal of Cancer logoLink to British Journal of Cancer
. 1991 Aug;64(2):243–246. doi: 10.1038/bjc.1991.284

The paradoxical effects of somatostatin on the bioactivity and production of cytotoxins derived from human peripheral blood mononuclear cells.

S Yousefi 1, N Vaziri 1, G Carandang 1, W Le 1, R Yamamoto 1, G Granger 1, J Ocariz 1, T Cesario 1
PMCID: PMC1977502  PMID: 1679996

Abstract

Somatostatin (SMS), a naturally occurring peptide is known to inhibit the production of certain protein molecules and to diminish the ability of peripheral blood mononuclear cells to proliferate. We tested the effects of three forms of SMS on the bioactivity of both lymphotoxin (LT) and tumour necrosis factor (TNF). We also tested the effects of these agents on production of cytotoxins by peripheral blood mononuclear cells. We found the 28 amino acid form of SMS significantly enhanced the bioactivity of both LT and TNF (10(-9) M concentration) when tested in mouse L cells. The 14 amino acid form of SMS enhanced LT (10(-9) M concentration) activity but not TNF activity. The first 14 amino acid form of SMS-28 (amino terminal) did not affect bioactivity of the cytotoxin. In contrast, the naturally occurring 14 amino acid form of SMS (10(-8) M concentration) significantly diminished production of cytotoxin by human peripheral blood mononuclear cells. Cytotoxin produced by the latter was shown to be a combination of both LT and TNF. Similarly after SMS exposure, the cytotoxin produced remained a mixture of LT and TNF in roughly similar proportions. It thus appears that certain forms of SMS can enhance the bioactivity of cytotoxins, but at the same time decrease the production of these cytotoxins.

Full text

PDF
243

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Berenbaum M. C., Fluck P. A., Hurst N. P. Depression of lymphocyte responses after surgical trauma. Br J Exp Pathol. 1973 Dec;54(6):597–607. [PMC free article] [PubMed] [Google Scholar]
  2. Brazeau P., Vale W., Burgus R., Ling N., Butcher M., Rivier J., Guillemin R. Hypothalamic polypeptide that inhibits the secretion of immunoreactive pituitary growth hormone. Science. 1973 Jan 5;179(4068):77–79. doi: 10.1126/science.179.4068.77. [DOI] [PubMed] [Google Scholar]
  3. Browning J., Ribolini A. Studies on the differing effects of tumor necrosis factor and lymphotoxin on the growth of several human tumor lines. J Immunol. 1989 Sep 15;143(6):1859–1867. [PubMed] [Google Scholar]
  4. Cesario T. C., McCloskey M., Carandang G., Yousefi S., Chiu J., Vaziri N. Calcium and the production of interferon by human peripheral blood mononuclear cells. J Interferon Res. 1988 Dec;8(6):783–792. doi: 10.1089/jir.1988.8.783. [DOI] [PubMed] [Google Scholar]
  5. Cuturi M. C., Murphy M., Costa-Giomi M. P., Weinmann R., Perussia B., Trinchieri G. Independent regulation of tumor necrosis factor and lymphotoxin production by human peripheral blood lymphocytes. J Exp Med. 1987 Jun 1;165(6):1581–1594. doi: 10.1084/jem.165.6.1581. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Goeddel D. V., Aggarwal B. B., Gray P. W., Leung D. W., Nedwin G. E., Palladino M. A., Patton J. S., Pennica D., Shepard H. M., Sugarman B. J. Tumor necrosis factors: gene structure and biological activities. Cold Spring Harb Symp Quant Biol. 1986;51(Pt 1):597–609. doi: 10.1101/sqb.1986.051.01.072. [DOI] [PubMed] [Google Scholar]
  7. Goetzl E. J., Chernov-Rogan T., Cooke M. P., Renold F., Payan D. G. Endogenous somatostatin-like peptides of rat basophilic leukemia cells. J Immunol. 1985 Oct;135(4):2707–2712. [PubMed] [Google Scholar]
  8. Gorden P., Comi R. J., Maton P. N., Go V. L. NIH conference. Somatostatin and somatostatin analogue (SMS 201-995) in treatment of hormone-secreting tumors of the pituitary and gastrointestinal tract and non-neoplastic diseases of the gut. Ann Intern Med. 1989 Jan 1;110(1):35–50. doi: 10.7326/0003-4819-110-1-35. [DOI] [PubMed] [Google Scholar]
  9. Gustavsson S., Lundqvist G. Inhibition of pancreatic somatostatin release in response to glucose. Biochem Biophys Res Commun. 1978 Jun 29;82(4):1229–1235. doi: 10.1016/0006-291x(78)90319-4. [DOI] [PubMed] [Google Scholar]
  10. Lewis J. E., Carmack C. E., Yamamoto R., Granger G. A. Antibodies against human lymphokines: I. Methods for induction of antibodies capable of neutralizing stable (alpha) and unstable (beta) lymphotoxins released in vitro by activated human lymphocytes. J Immunol Methods. 1977;14(2):163–176. doi: 10.1016/0022-1759(77)90006-0. [DOI] [PubMed] [Google Scholar]
  11. Mascardo R. N., Barton R. W., Sherline P. Somatostatin has an antiproliferative effect on concanavalin A-activated rat thymocytes. Clin Immunol Immunopathol. 1984 Oct;33(1):131–138. doi: 10.1016/0090-1229(84)90299-x. [DOI] [PubMed] [Google Scholar]
  12. McCann S. M., Krulich L., Negro-Vilar A., Ojeda S. R., Vijayan E. Regulation and function of panhibin (somatostatin). Adv Biochem Psychopharmacol. 1980;22:131–143. [PubMed] [Google Scholar]
  13. Pace C. S., Tarvin J. T. Somatostatin: mechanism of action in pancreatic islet beta-cells. Diabetes. 1981 Oct;30(10):836–842. doi: 10.2337/diab.30.10.836. [DOI] [PubMed] [Google Scholar]
  14. Paul N. L., Ruddle N. H. Lymphotoxin. Annu Rev Immunol. 1988;6:407–438. doi: 10.1146/annurev.iy.06.040188.002203. [DOI] [PubMed] [Google Scholar]
  15. Pawlikowski M., Stepien H., Kunert-Radek J., Schally A. V. Effect of somatostatin on the proliferation of mouse spleen lymphocytes in vitro. Biochem Biophys Res Commun. 1985 May 31;129(1):52–55. doi: 10.1016/0006-291x(85)91401-9. [DOI] [PubMed] [Google Scholar]
  16. Payan D. G., Hess C. A., Goetzl E. J. Inhibition by somatostatin of the proliferation of T-lymphocytes and Molt-4 lymphoblasts. Cell Immunol. 1984 Apr 1;84(2):433–438. doi: 10.1016/0008-8749(84)90117-5. [DOI] [PubMed] [Google Scholar]
  17. Reichlin S. Somatostatin. N Engl J Med. 1983 Dec 15;309(24):1495–1501. doi: 10.1056/NEJM198312153092406. [DOI] [PubMed] [Google Scholar]
  18. Schally A. V., Huang W. Y., Chang R. C., Arimura A., Redding T. W., Millar R. P., Hunkapiller M. W., Hood L. E. Isolation and structure of pro-somatostatin: a putative somatostatin precursor from pig hypothalamus. Proc Natl Acad Sci U S A. 1980 Aug;77(8):4489–4493. doi: 10.1073/pnas.77.8.4489. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Schally A. V. Oncological applications of somatostatin analogues. Cancer Res. 1988 Dec 15;48(24 Pt 1):6977–6985. [PubMed] [Google Scholar]
  20. Stanisz A. M., Befus D., Bienenstock J. Differential effects of vasoactive intestinal peptide, substance P, and somatostatin on immunoglobulin synthesis and proliferations by lymphocytes from Peyer's patches, mesenteric lymph nodes, and spleen. J Immunol. 1986 Jan;136(1):152–156. [PubMed] [Google Scholar]
  21. Wagner H., Hengst K., Zierden E., Gerlach U. Investigations of the antiproliferative effect of somatostatin in man and rats. Metabolism. 1978 Sep;27(9 Suppl 1):1381–1386. doi: 10.1016/0026-0495(78)90079-3. [DOI] [PubMed] [Google Scholar]
  22. Wünsch E., Jaeger E., Moroder L., Peggion E., Palumbo M. Somatostatin-28: a conformational analysis. Biopolymers. 1981 Aug;20(8):1741–1745. doi: 10.1002/bip.1981.360200813. [DOI] [PubMed] [Google Scholar]
  23. Yousefi S., Ghazinouri A., Vaziri N., Tilles J., Carandang G., Cesario T. The effect of somatostatin on the production of human interferons by mononuclear cells. Proc Soc Exp Biol Med. 1990 Jun;194(2):114–118. doi: 10.3181/00379727-194-43065. [DOI] [PubMed] [Google Scholar]

Articles from British Journal of Cancer are provided here courtesy of Cancer Research UK

RESOURCES