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Possible Mechanisms of Action of the Anticarcinogenic Protease Inhibitors

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Anticarcinogenesis and Radiation Protection

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.

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References

  1. W. Troll, A. Klassen, and A. Janoff, Tumorigenesis in mouse skin: Inhibition by synthetic inhibitors of proteases. Science, 169, 1211–1213 (1970).

    Article  PubMed  CAS  Google Scholar 

  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).

    PubMed  CAS  Google Scholar 

  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).

    Article  PubMed  CAS  Google Scholar 

  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).

    Article  PubMed  CAS  Google Scholar 

  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).

    Article  PubMed  CAS  Google Scholar 

  6. P. Correa, Epidemiological correlations between diet and cancer frequency. Cancer Res. 41, 3685–3690 (1981).

    PubMed  CAS  Google Scholar 

  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).

    Article  PubMed  CAS  Google Scholar 

  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).

    PubMed  CAS  Google Scholar 

  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. D. E. Mullins and S. T. Rohrlich, The role of proteinases in cellular invasiveness. Biochim. Biophys. Acta, 695, 177–214 (1983).

    PubMed  CAS  Google Scholar 

  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).

    Article  PubMed  Google Scholar 

  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).

    Article  PubMed  Google Scholar 

  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).

    Article  PubMed  CAS  Google Scholar 

  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).

    Article  CAS  Google Scholar 

  15. M. B. Sporn and A. B. Roberts, Autocrine growth factors and cancer. Nature 313, 745–747 (1985).

    Article  PubMed  CAS  Google Scholar 

  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).

    PubMed  CAS  Google Scholar 

  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).

    PubMed  CAS  Google Scholar 

  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).

    Article  PubMed  CAS  Google Scholar 

  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).

    Article  PubMed  CAS  Google Scholar 

  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).

    PubMed  CAS  Google Scholar 

  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).

    PubMed  CAS  Google Scholar 

  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).

    Article  PubMed  CAS  Google Scholar 

  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).

    Article  PubMed  CAS  Google Scholar 

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© 1987 Plenum Press, New York

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Yavelow, J., Kraft, J.H., Schepis, L. (1987). Possible Mechanisms of Action of the Anticarcinogenic Protease Inhibitors. In: Cerutti, P.A., Nygaard, O.F., Simic, M.G. (eds) Anticarcinogenesis and Radiation Protection. Springer, Boston, MA. https://doi.org/10.1007/978-1-4615-6462-1_44

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  • DOI: https://doi.org/10.1007/978-1-4615-6462-1_44

  • Publisher Name: Springer, Boston, MA

  • Print ISBN: 978-1-4615-6464-5

  • Online ISBN: 978-1-4615-6462-1

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