Skip to main content
NCBI home page
British Journal of Cancer logoLink to British Journal of Cancer
. 1988 Aug;58(2):147–151. doi: 10.1038/bjc.1988.182

Inhibition of mitogen stimulated growth of human colon cancer cells by interferon.

A W Hamburger 1, M E Condon 1, K O'Donnell 1
PMCID: PMC2246752  PMID: 3166905

Abstract

Recombinant human interferon alpha inhibits growth of a human colon cancer cell line, Colo 205. To explore the mechanisms of IFN induced growth inhibition, quiescent Colo 205 cells were stimulated to proliferate in serum-free media by defined growth factors. Addition of insulin, transferrin and selenium (ITS) stimulated DNA synthesis, as measured by 3H-thymidine incorporation, in a dose-dependent manner. IFN-alpha (at concentrations greater than 100 U ml-1) inhibited ITS stimulated DNA synthesis by 63%. Inhibition of cell cycle traverse was confirmed by flow cytometric analysis. Although IFN inhibited growth of ITS-treated cells, steady state levels of c-myc mRNA remained above levels observed in unstimulated cells. IFN inhibited DNA synthesis only when added prior to mitogen stimulation. IFN, added 6 h after exposure of quiescent cells to ITS, failed to inhibit cell growth. Addition of increasing concentrations of ITS failed to overcome the IFN-induced growth inhibition. These results suggest IFN may inhibit cell growth in part by antagonizing the action of growth factors.

Full text

PDF
147

Images in this article

149Figure 4
on p.149

Selected References

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

  1. Chirgwin J. M., Przybyla A. E., MacDonald R. J., Rutter W. J. Isolation of biologically active ribonucleic acid from sources enriched in ribonuclease. Biochemistry. 1979 Nov 27;18(24):5294–5299. doi: 10.1021/bi00591a005. [DOI] [PubMed] [Google Scholar]
  2. Clemens M. J., McNurlan M. A. Regulation of cell proliferation and differentiation by interferons. Biochem J. 1985 Mar 1;226(2):345–360. doi: 10.1042/bj2260345. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Dalla-Favera R., Martinotti S., Gallo R. C., Erikson J., Croce C. M. Translocation and rearrangements of the c-myc oncogene locus in human undifferentiated B-cell lymphomas. Science. 1983 Feb 25;219(4587):963–967. doi: 10.1126/science.6401867. [DOI] [PubMed] [Google Scholar]
  4. Denz H., Lechleitner M., Marth C., Daxenbichler G., Gastl G., Braunsteiner H. Effect of human recombinant alpha-2- and gamma-interferon on the growth of human cell lines from solid tumors and hematologic malignancies. J Interferon Res. 1985 Winter;5(1):147–157. doi: 10.1089/jir.1985.5.147. [DOI] [PubMed] [Google Scholar]
  5. Einat M., Resnitzky D., Kimchi A. Close link between reduction of c-myc expression by interferon and, G0/G1 arrest. Nature. 1985 Feb 14;313(6003):597–600. doi: 10.1038/313597a0. [DOI] [PubMed] [Google Scholar]
  6. Heyns A. D., Eldor A., Vlodavsky I., Kaiser N., Fridman R., Panet A. The antiproliferative effect of interferon and the mitogenic activity of growth factors are independent cell cycle events. Studies with vascular smooth muscle cells and endothelial cells. Exp Cell Res. 1985 Dec;161(2):297–306. doi: 10.1016/0014-4827(85)90087-4. [DOI] [PubMed] [Google Scholar]
  7. Jasny B. R., Fried J., Tamm I. The effects of treatment with human beta-interferon on the stimulation of thymidine uptake and DNA synthesis by colchicine in human fibroblasts. J Interferon Res. 1985 Spring;5(2):239–246. doi: 10.1089/jir.1985.5.239. [DOI] [PubMed] [Google Scholar]
  8. Kohase M., Henriksen-DeStefano D., May L. T., Vilcek J., Sehgal P. B. Induction of beta 2-interferon by tumor necrosis factor: a homeostatic mechanism in the control of cell proliferation. Cell. 1986 Jun 6;45(5):659–666. doi: 10.1016/0092-8674(86)90780-4. [DOI] [PubMed] [Google Scholar]
  9. Krishan A. Rapid flow cytofluorometric analysis of mammalian cell cycle by propidium iodide staining. J Cell Biol. 1975 Jul;66(1):188–193. doi: 10.1083/jcb.66.1.188. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Lin S. L., Kikuchi T., Pledger W. J., Tamm I. Interferon inhibits the establishment of competence in Go/S-phase transition. Science. 1986 Jul 18;233(4761):356–359. doi: 10.1126/science.3726533. [DOI] [PubMed] [Google Scholar]
  11. Lin S. L., Ts'o P. O., Hollenberg M. D. The effects of interferon on epidermal growth factor action. Biochem Biophys Res Commun. 1980 Sep 16;96(1):168–174. doi: 10.1016/0006-291x(80)91196-1. [DOI] [PubMed] [Google Scholar]
  12. Oleszak E., Inglot A. D. Platelet-derived growth factor (PDGF) inhibits antiviral and anticellular actin of interferon in synchronized mouse or human cells. J Interferon Res. 1980 Fall;1(1):37–48. doi: 10.1089/jir.1980.1.37. [DOI] [PubMed] [Google Scholar]
  13. Paganelli K. A., Evans S. S., Han T., Ozer H. B cell growth factor-induced proliferation of hairy cell lymphocytes and inhibition by type I interferon in vitro. Blood. 1986 Apr;67(4):937–942. [PubMed] [Google Scholar]
  14. Pfeffer L. M., Donner D. B., Tamm I. Interferon-alpha down-regulates insulin receptors in lymphoblastoid (Daudi) cells. Relationship to inhibition of cell proliferation. J Biol Chem. 1987 Mar 15;262(8):3665–3670. [PubMed] [Google Scholar]
  15. Resnitzky D., Yarden A., Zipori D., Kimchi A. Autocrine beta-related interferon controls c-myc suppression and growth arrest during hematopoietic cell differentiation. Cell. 1986 Jul 4;46(1):31–40. doi: 10.1016/0092-8674(86)90857-3. [DOI] [PubMed] [Google Scholar]
  16. Scheithauer W., Temsch E. M., Schieder K., Funovics H., Schiessel R., Grabner G. In vitro phase II trial of recombinant interferon alpha-2 in gastrointestinal cancer. Int J Cell Cloning. 1985 Jul;3(4):188–198. doi: 10.1002/stem.5530030401. [DOI] [PubMed] [Google Scholar]
  17. Shipley G. D., Childs C. B., Volkenant M. E., Moses H. L. Differential effects of epidermal growth factor, transforming growth factor, and insulin on DNA and protein synthesis and morphology in serum-free cultures of AKR-2B cells. Cancer Res. 1984 Feb;44(2):710–716. [PubMed] [Google Scholar]
  18. Taylor-Papadimitriou J., Balkwill F., Ebsworth N., Rozengurt E. Antiviral and antiproliferative effects of interferons in quiescent fibroblasts are dissociable. Virology. 1985 Dec;147(2):405–412. doi: 10.1016/0042-6822(85)90142-4. [DOI] [PubMed] [Google Scholar]
  19. Taylor-Papadimitriou J., Shearer M., Rozengurt E. Inhibitory effect of interferon on cellular DNA synthesis: modulation by pure mitogenic factors. J Interferon Res. 1981;1(3):401–409. doi: 10.1089/jir.1981.1.401. [DOI] [PubMed] [Google Scholar]
  20. Tominaga S., Lengyel P. beta-Interferon alters the pattern of proteins secreted from quiescent and platelet-derived growth factor-treated BALB/c-3T3 cells. J Biol Chem. 1985 Feb 25;260(4):1975–1978. [PubMed] [Google Scholar]
  21. Zoon K. C., Karasaki Y., zur Nedden D. L., Hu R. Q., Arnheiter H. Modulation of epidermal growth factor receptors by human alpha interferon. Proc Natl Acad Sci U S A. 1986 Nov;83(21):8226–8230. doi: 10.1073/pnas.83.21.8226. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Zullo J. N., Cochran B. H., Huang A. S., Stiles C. D. Platelet-derived growth factor and double-stranded ribonucleic acids stimulate expression of the same genes in 3T3 cells. Cell. 1985 Dec;43(3 Pt 2):793–800. doi: 10.1016/0092-8674(85)90252-1. [DOI] [PubMed] [Google Scholar]

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

RESOURCES