Advertisement

Possible Mechanisms of Action of the Anticarcinogenic Protease Inhibitors

  • Jonathan Yavelow
  • Judith H. Kraft
  • Lorraine Schepis

Abstract

Protease inhibitors have been shown to possess anticarcinogenic properties. Two synthetic protease inhibitors, tosyl phenylethyl chloro-methyl ketone (TPCK) and tosylarginine methylester (a competitive trypsin substrate), have been demonstrated to block the formation of skin tumors promoted with TPA in mice (1). These studies were repeated using the actinomycete-derived protease inhibitor leupeptin (2), thus establishing an in vivo basis for the involvement of proteases in the mechanism of carcinogenesis.

Keywords

Detergent Extraction Crude Membrane Fraction Discontinuous Sucrose Density Gradient Synthetic Protease Inhibitor Tyrosine Ethyl Ester 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    W. Troll, A. Klassen, and A. Janoff, Tumorigenesis in mouse skin: Inhibition by synthetic inhibitors of proteases. Science, 169, 1211–1213 (1970).PubMedCrossRefGoogle Scholar
  2. 2.
    M. Hozumi, M. Ogawa, T. Sugimura, T. Takenchi, and H. Umezawa, Inhibition of tumorigenesis in mouse skin by leupeptin, a protease inhibitor from actinomycetes. Cancer Res. 32, 1725–1728 (1972).PubMedGoogle Scholar
  3. 3.
    J. G. Corasanti, G. H. Hobika, and G. Markus, Interference with dimethylhydrazine induction of colon tumors in mice by e-aminocaproic acid. Science, 216, 1020–1021 (1982).PubMedCrossRefGoogle Scholar
  4. 4.
    W. Troll, R. Wiesner, C. J. Shellabarger, S. Holtzman, and J. P. Stone, Soybean diet lowers breast tumor incidence in irradiated rats. Carcinogenesis, 1, 469–472 (1980).PubMedCrossRefGoogle Scholar
  5. 5.
    F. F. Becker, Inhibition of spontaneous hepatocarcinogenesis in C3H/HeN mice by Edi Pro A, an isolated soy protein. Carcinogenesis, 2, 1213–1214 (1981).PubMedCrossRefGoogle Scholar
  6. 6.
    P. Correa, Epidemiological correlations between diet and cancer frequency. Cancer Res. 41, 3685–3690 (1981).PubMedGoogle Scholar
  7. 7.
    B. Armstrong and R. Doll, Environmental factors and cancer incidence and mortality in different countries with special reference to dietary practices. Int. J. Cancer, 15. 617–631 (1975).PubMedCrossRefGoogle Scholar
  8. 8.
    J. Yavelow, T. Finlay, A. R. Kennedy, and W. Troll, Bowman-Birk soybean protease inhibitor as an anticarcinogen. Cancer Res. 43, 2454s-2459s (1983).PubMedGoogle Scholar
  9. 9.
    J. P. Quigley, Proteolytic enzymes of normal and malignant cells. In:Surfaces of Normal and Malignant Cells (R. O. Hynes, Ed.) pp. 247–285. Sussex, England: John Wiley and Sons (1979).Google Scholar
  10. 10.
    D. E. Mullins and S. T. Rohrlich, The role of proteinases in cellular invasiveness. Biochim. Biophys. Acta, 695, 177–214 (1983).PubMedGoogle Scholar
  11. 11.
    J. O’Donnell-Tormey and J. P. Quigley, Inhibition of plasminogen activatory release from transformed chicken fibroblasts by a protease inhibitor. Cell, 27, 85–95 (1981).PubMedCrossRefGoogle Scholar
  12. 12.
    J. O’Donnell-Tormey and J. P. Quigley, Detection and partial characterization of a chymostatin-sensitive endopeptidase in transformed fibroblasts. Proc. Natl. Acad. Sci. USA, 80, 344–348 (1983).PubMedCrossRefGoogle Scholar
  13. 13.
    J. Yavelow, M. Collins, Y. Birk, W. Troll and A. R. Kennedy, Nanomolar concentrations of Bowman-Birk soybean protease inhibitor suppress X-ray-induced transformation in vitro. Proc. Natl. Acad. Sci. USA, 82, 5395–5399 (1985).PubMedCrossRefGoogle Scholar
  14. 14.
    A. R. Kennedy, The conditions for the modification of radiation transformation in vitro by a tumor promoter and protease inhibitors. Carcinogenesis (Lond.), 6, 1441–1445, (1985).CrossRefGoogle Scholar
  15. 15.
    M. B. Sporn and A. B. Roberts, Autocrine growth factors and cancer. Nature 313, 745–747 (1985).PubMedCrossRefGoogle Scholar
  16. 16.
    L. Waxman, J. M. Fagan, K. Tanaka and A. L. Goldberg, A soluble ATP-dependent system for protein degradation from murine erythroleukemia cells. J. Biol. Chem. 260, 11994–12000(1985).PubMedGoogle Scholar
  17. 17.
    J. J. Baldassare, S. Bakshian, M. A. Knipp, and G. J. Fisher, Inhibition of fibrinogen receptor expression and serotonin release by leupeptin and antipain. J. Biol. Chem. 260. 10531–10535 (1985).PubMedGoogle Scholar
  18. 18.
    A. R. Kennedy, B. S. Radner, and H. Nagasawa, Protease inhibitors reduce the frequency of spontaneous chromosome abnormalities in cells from patients with Bloom’s syndrome. Proc. Natl. Acad. Sci. USA, 81 1827–1830 (1984).PubMedCrossRefGoogle Scholar
  19. 19.
    A. L. Jochen and P. Berhanu, Chymotrypsin substrate analogues inhibit endocytosis of insulin and insulin receptors in adipocytes. J. Cell Biol. 103, 1807–1816 (1986).PubMedCrossRefGoogle Scholar
  20. 20.
    J. Yavelow, M. Caggana, and K. A. Beck, Proteases occurring in the cell membrane: A possible cell receptor for the Bowman-Birk type of protease inhibitors. Cancer Res. 47, 1598–1601 (1987).PubMedGoogle Scholar
  21. 21.
    J. Yavelow, C. Scott, and T. C. Mayer, Fluorescent visualization of binding and internalization of the anticarcinogenic Bowman-Birk type protease inhibitors in transformed fibroblasts. Cancer Res. 47, 1602–1607 (1987).PubMedGoogle Scholar
  22. 22.
    J. P. Quigley, Association of a protease (plasminogen activator) with a specific membrane fraction isolated from transformed cells. J. Cell Biol. 71, 472–486 (1976).PubMedCrossRefGoogle Scholar
  23. 23.
    M. Bradford, A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal. Biochem. 72, 248–254 (1976).PubMedCrossRefGoogle Scholar

Copyright information

© Plenum Press, New York 1987

Authors and Affiliations

  • Jonathan Yavelow
    • 1
  • Judith H. Kraft
    • 1
  • Lorraine Schepis
    • 1
  1. 1.Department of BiologyRider CollegeLawrencevilleUSA

Personalised recommendations