Prevention of Cancer by Vitamin B3 (Nicotinamide and Nicotinic Acid)

A Protease Inhibitor Available in Pure Form
  • Walter Troll


Protease inhibitors (PIs) occur widely throughout plant and animal systems. Their role in preventing diseases in animals includes controlling blood clotting and contributing to the prevention of cancer. A workshop organized by the National Cancer Institute on “Protease Inhibitors as Cancer Chemopreventive Agents” concluded with the following recommendations for future research: (1) research and development of sources of PIs, (2) analysis of human foods for PI content, (3) evaluation of cancer incidence data in relation to PI content and characteristics in the diet of human populations, (4) animal studies on the efficacy of PIs in cancer prevention, and (5) studies on the mechanism of action of anticarcinogenic PIs (Troll et al., 1987).


Tumor Promotion Mouse Skin Chloromethyl Ketone Cancer Chemopreventive Agent Kunitz Soybean Trypsin Inhibitor 
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  1. Armstrong, B., and Doll, R., 1975, Environmental factors and cancer incidence and mortality in different countries, with special reference to dietary factors, Int. J. Cancer 15:617–631.PubMedCrossRefGoogle Scholar
  2. Badwey, J. A., and Karnovsky, M. L., 1980, Active oxygen species and the functions of phagocytic leukocytes, Annu. Rev. Biochem. 49:695–696.PubMedCrossRefGoogle Scholar
  3. Becker, F. F., 1981, Inhibition of spontaneous hepatocarcinogenesis in C3H/HeN mice by Edipro A, an isolated soy protein. Carcinogenesis 2:1213–1214.PubMedCrossRefGoogle Scholar
  4. Berger, N. A., 1985, Symposium: Cellular response to DNA damage: The role of poly(ADP-ribose), Radiat. Res. 101:4–15.PubMedCrossRefGoogle Scholar
  5. Billings, P. C., Shuin, T., Lillehaug, J., Miura, T., Roy-Burman, P., and Landolph, J. R., 1987, Enhanced expression and state of the c-myc oncogene in chemically and X-ray transformed C3H/10T1/2 Cl 8 mouse embryo fibroblasts, Cancer Res. 47:3643–3649.PubMedGoogle Scholar
  6. Carroll, K. K., 1975, Experimental evidence of dietary factors and hormone-dependent cancers, Cancer Res. 35:3374–3383.PubMedGoogle Scholar
  7. Chang, J. D., Billings, P. C., and Kennedy, A. R., 1985, C-myc expression is reduced in antipain-treated proliferating C3H10T1/2 cells, Biochem. Biophys. Res. Commun. 133:830–835.PubMedCrossRefGoogle Scholar
  8. Corasanti, J. G., Hobika, G. H., and Markus, G., 1982, Interference with dimethylhydrazine induction of colon tumors in mice by ε-aminocaproic acid, Science 216:1020–1021.PubMedCrossRefGoogle Scholar
  9. Correa, P., 1981, Epidemiological correlations between diet and cancer frequency, Cancer Res. 41:3685–3690.PubMedGoogle Scholar
  10. Cox, L. R., Motz, J., Troll, W., and Garte, S. J., 1991, Effects of retinolc acid on NIH3T3 cell transformation by the H-ras oncogene, J. Cancer Res. Clin. Oncol. 117:102–108.PubMedCrossRefGoogle Scholar
  11. Davidson, D., Garte, S., and Troll, W. 1986, H-ras oncogene DNA affects embryonic development in the sea urchin, Biol. Bull. 171:472.Google Scholar
  12. Diamond, A. M., Der, C. J., and Schwartz, J. L., 1989, Alterations in transformation efficiency by the ADPRT-inhibitor 3-aminobenzamide are oncogene specific, Carcinogenesis 10:383–385.PubMedCrossRefGoogle Scholar
  13. Fantone, J. C., and Ward, P. A., 1982, Role of oxygen-derived free radicals and metabolites in leukocyte-dependent inflammatory reactions, Am. J. Pathol. 107:397–418.Google Scholar
  14. Formisano, J., Troll, W., and Sugimura, T., 1983, Superoxide response induced by indole alkaloid tumor promoters, Ann. N.Y. Acad. Sci. 407:429–431.CrossRefGoogle Scholar
  15. Frenkel, K., and Chrzan, K., 1987, Hydrogen peroxide formation and DNA base modification by tumor promoter-activated polymorphonuclear leukocytes, Carcinogenesis 8:455–460.PubMedCrossRefGoogle Scholar
  16. Frenkel, K., Chrzan, K., Ryan, C., Wiesner, R., and Troll, W., 1987, Chymotrypsin-specific protease inhibitors decrease H2O2 formation by activated human polymorphonuclear leukocytes, Carcinogenesis 8:1207–1212.PubMedCrossRefGoogle Scholar
  17. Fujiki, H., Suganuma, M., Supuri, H., Yoshizawa, S., Takagi, K., and Kobaya, M., 1989, Sarcophytols A and B inhibit tumor promotion by teleocidin in two-stage carcinogenesis in mouse skin, J. Cancer Res. Clin. Oncol. 115:25–28.PubMedCrossRefGoogle Scholar
  18. Garte, S. J., Currie, D. D., and Troll, W., 1987, Inhibition of H-ras oncogene transformation of NIH 3T3 cells by protease inhibitors. Cancer Res. 47:3159–3162.PubMedGoogle Scholar
  19. Garte, S. J., Burns, F. J., Ashkenazi-Kimmel, T., Felber, M., and Sawey, M. J., 1990, Amplification of the c-myc oncogene during progression of radiation-induced rat skin tumors, Cancer Res. 50:3073–3077.PubMedGoogle Scholar
  20. Gillam, S. S., Watson, J. G., and Chaykin, S., 1973, Nicotinamide deamidase from rabbit liver. III. Inhibition and sedimentation, Arch. Biochem. Biophys. 157:268–281.PubMedCrossRefGoogle Scholar
  21. Greengard, P., Petrack, B., and Kalinsky, H. J., 1969, Identification of hormonally controlled endogenous inhibitor of liver nicotinamide deamidase, Biochim. Biophys. Acta 184:148–153.PubMedCrossRefGoogle Scholar
  22. Hozumi, M., Ogawa, M, Sugimura, T., Takeuchi, T., and Umezawa, H., 1972, Inhibition of tumorigenesis in mouse skin by leupeptin, a protease inhibitor from Actinomycetes, Cancer Res. 32:1725–1729.PubMedGoogle Scholar
  23. Kinzel, V., Fürstenberger, G., Loehrke, H., and Marks, F., 1986, Three-stage tumorigenesis in mouse skin: DNA synthesis as a prerequisite for the conversion stage induced by TPA prior to initiation, Carcinogenesis 7:779–782.PubMedCrossRefGoogle Scholar
  24. Narisawa, T., Takahashi, M., Niwa, M., Fukaura, Y., and Fujiki, H., 1989, Inhibition of methylnitrosourea-induced large bowel cancer development in rats by sarcophytol A, a product from a marine soft-coral Sarcophyton glaucum, Cancer Res. 49:3287–3289.PubMedGoogle Scholar
  25. Nishizuka, Y, 1984, The role of protein kinase C in cell surface signal transduction and tumor promotion, Nature 308:693–698.PubMedCrossRefGoogle Scholar
  26. Penn, A., Garte, S. J., Warren, L., Nesta, D., and Mindich, B., 1986, Transforming gene in human atherosclerotic plaque DNA, Proc. Natl. Acad. Sci. USA 83:7951–7955.PubMedCrossRefGoogle Scholar
  27. Phillips, R. L., 1975, Role of life-style and dietary habits in risk of cancer among Seventh-Day Adventists, Cancer Res. 35:3513–3522.PubMedGoogle Scholar
  28. Quintanilla, M., Brown, K., Ramsden, M., and Balmain, A., 1986, Carcinogen-specific mutation and amplification of Ha-ras during mouse skin carcinogenesis, Nature 322:78–80.PubMedCrossRefGoogle Scholar
  29. Sakamoto, M., Yanagi, S., and Kamiya, T., 1987, Inhibitory effects of niacin and its analogues on induction of ornithine decarboxylase activity by diethylnitrosamine in rat liver, Biochem. Pharmacol. 36:3015–3019.PubMedCrossRefGoogle Scholar
  30. Schuster, M. G., Enriquez, P. M., Curran, P., Cooperman, B. S., and Rubin, H., 1992, Regulation of neutrophil superoxide by antichymotrypsin-chymotrypsin complexes, J. Biol. Chem. 267:5056–5059.PubMedGoogle Scholar
  31. Slaga, T. J., Klein-Szanto, A. J. P., Triplett, L. L., Yotti, L. P., and Trosko, J. E., 1981, Skin tumor promoting activity of benzoyl peroxide, a widely used free radical-generating compound, Science 213:1023–1025.PubMedCrossRefGoogle Scholar
  32. Troll, W., and Corcoran, G., 1989, Nicotinamide suppresses Arbacia punctulata development, Biol. Bull. 177:317.Google Scholar
  33. Troll, W., Klassen, A., and Janoff, A., 1970, Tumorigenesis in mouse skin: Inhibition by synthetic inhibitors of proteases. Science 169:1211–1213.PubMedCrossRefGoogle Scholar
  34. Troll, W., Belman, S., Wiesner, R., and Shellabarger, C. J., 1979, Protease action in carcinogenesis, in: Biological Function of Proteinases (H. Holzer and H. Tschesche, eds.), Springer-Verlag, Berlin, pp. 165–170.CrossRefGoogle Scholar
  35. Troll, W., Wiesner, R., Shellabarger, C. J., Holtzman, S., and Stone, J. P., 1980, Soybean diet lowers breast tumor incidence in irradiated rats, Carcinogenesis 1:469–472.PubMedCrossRefGoogle Scholar
  36. Troll, W., Wiesner, R., and Frenkel, K., 1987, Anticarcinogenic action of protease inhibitors, Adv. Cancer Res. 49:265–283.PubMedCrossRefGoogle Scholar
  37. Troll, W., Garte, S., and Frenkel, K., 1990, Suppression of tumor promotion by inhibitor of poly(ADP)ribose formation, in: Antimutagene sis and Anticarcinogenesis Mechanisms II (Y Kuroda, D. M. Shankel, and M. D. Waters, eds.), Plenum Press, New York, pp. 225–232.CrossRefGoogle Scholar
  38. Troll, W., Belman, S., and Cohen, L. A., 1992, Nicotinic acid supplemented diets suppress tumor promotion, Proc. Am. Assoc. Cancer Res. 33:131.Google Scholar
  39. Udenfriend, S., Stein, S., Böhlen, P., Dairman, W., Leimgruber, W., and Weigele, M., 1972, Fluorescamine: A reagent for assay of amino acids, peptides, proteins and primary amines in the picomole range, Science 178:871–872.PubMedCrossRefGoogle Scholar
  40. Wattenberg, L. W. 1985, Chemoprevention of cancer, Cancer Res. 45:1–8.PubMedCrossRefGoogle Scholar
  41. Weed, H. G., McGandy, R. B., and Kennedy, A. R., 1985, Protection against dimethylhydrazine-induced adenomatous tumors of the mouse colon by the dietary addition of an extract of soybeans containing the Bowman-Birk protease inhibitor, Carcinogenesis 6:1239–1241.PubMedCrossRefGoogle Scholar
  42. Wei, H., and Frenkel, K., 1992, Suppression of tumor promoter-induced oxidative events and DNA damage in vivo by sarcophytol A: A possible mechanism of anti-promotion, Cancer Res. 5:2298–2303.Google Scholar
  43. Weitberg, A. B., 1989, Effect of nicotinic acid supplementation in vivo on oxygen radical-induced genetic damage in human lymphocytes, Mutat. Res. 216:197–201.PubMedCrossRefGoogle Scholar
  44. Wynder, E., Mabuchi, K., and Whitmore, W., 1971, Epidemiology of cancer of the prostate, Cancer 28:344–360.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 1993

Authors and Affiliations

  • Walter Troll
    • 1
  1. 1.Department of Environmental MedicineNew York University Medical CenterNew YorkUSA

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