Skip to main content
Log in

Evaluation of the potential of cancer chemopreventive activity mediated by inhibition of 12-O-tetradecanoyl phorbol 13-acetate-induced ornithine decarboxylase activity

  • Research Articles
  • Pharmacology & Toxicology
  • Published:
Archives of Pharmacal Research Aims and scope Submit manuscript

Abstract

In order to discover new cancer chemopreventive agents from natural or synthetic products, a structurally diverse class of chemopreventive agents was evaluated usingin vitro biomarker of inhibition of 12-O-tetradecanoylphorbol 13-acetate (TPA)-induced ornithine decarboxylase (ODC) activity in cultured mouse epidermal 308 (ME 308) cells. As a result, apigenin, benzylisothiocyanate, curcumin, diallyl disulfide,N-(4-hydroxyphenyl)retinamide (4-HPR), menadione, miconazole, nordihydroguaiaretic acid (NDGA) and phenethyl isothiocyanate showed potent inhibitory effects in this process. A chemically diverse group of compounds was included in the evaluation, such as flavonoids, retinoids, isothiocyanates, sulfur-containing compounds and phenolic antioxidant compounds. These data are suggestive to understand the cancer chemopreventive potential mediated by these substances.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References cited

  • Auvinen, M., Paasinen, A., Anderson, I. C. and Hölttä, E., Ornithine decarboxylase activity is critical for cell transformation.Nature, 360, 355–358 (1992).

    Article  PubMed  CAS  Google Scholar 

  • Brady, J. F., Li, D. C., Ishizaki, H. and Yang, C. S., Effect of diallyl sulfide on rat liver microsomal nitrosamine metabolism and other monooxygenase activities.Cancer Res., 48, 5937–5940 (1988).

    PubMed  CAS  Google Scholar 

  • Gilmour, S. K., Robertson, F. M., Megosh, L., OConnell, S. M., Mitchell, J. and OBrien, T. G., Induction of ornithine decarboxylase in specific subpopulations of murine epidermal cells following multiple exposures to 12-O-tetradecanoylphorbol-13-acetate, mezerein and ethyl phenylpropriolate.Carcinogenesis, 13, 51–56 (1992).

    Article  PubMed  CAS  Google Scholar 

  • Hayes, M.A., Rushmore, T.H. and Goldberg, M.T., Inhibition of hepatocarcinogenic responses to 1,2-dimethylhydrazine by diallyl sulfide, a component of garlic oil.Carcinogenesis, 8, 1155–1157 (1987).

    Article  PubMed  CAS  Google Scholar 

  • Huang, M.-T., Ho, C. T., Wang, Z. Y., Farraro, T., Finnegan-Olive, T., Lou, Y.R., Mitchell, J.M., Laskin, J.D., Yang, C.S. and Conney, A.H., Inhibitory effects of topical application of green tea polyphenol fraction on tumor initiation and promotion in mouse skin.Carcinogenesis, 13, 947–954 (1992).

    Article  PubMed  CAS  Google Scholar 

  • Huang, M.-T., Ma, W., Lu, Y.-P. Chang, R. L., Fisher, C., Manchand, P. S., Newmark, H. L. and Conney, A. H., Effects of curcumin, demethoxycurcumin, bisdemethoxycurcumin and tetrahydrocurcumin on 12-O-tetradecanoylphorbol 13-acetate-induced tumor promotion.Carcinogenesis, 16, 2493–2497 (1995).

    Article  PubMed  CAS  Google Scholar 

  • Huang, M.-T., Smart, R. C., Wong, C.-Q. and Conney, A. H., Inhibitory effect of curcumin, chlorogenic acid, caffeic acid, and ferulic acid on tumor promotion in mouse skin by 12-O-tetradecanoylphorbol-13-acetate.Cancer Res., 48, 5941–5946 (1988).

    PubMed  CAS  Google Scholar 

  • Kahana, C. and Nathans, D., Isolation of cloned cDNA encoding mammalian ornithine decarboxylase.Proc. Natl. Acad. Sci., USA, 81, 3645–3649 (1984).

    Article  PubMed  CAS  Google Scholar 

  • Katz, A. and Kahana, C., Transcriptional activation of mammalian ornithine decarboxylase during stimulated growth.Mol. Cell Biol., 7, 2641–2643 (1987).

    PubMed  CAS  Google Scholar 

  • Kelloff, G. J., Chemopreventive drug development: Perspectives and progress.Cancer Epidemiol. Biomarkers & Prev., 3, 85–98 (1994).

    CAS  Google Scholar 

  • Lee, S. K., Song, L., Mata-Greenwood, E., Kelloff, G. J., Steele, V. E. and Pezzuto, J. M., Modulation of in vitro biomarkers of the carcinogenic process by chemopreventive agents.Anticancer Res., 19, 35–44 (1999).

    PubMed  CAS  Google Scholar 

  • Lowry, O. H., Rosebrough, N. J., Farr, A. L. and Randall R. J., Protein measurement with the folin phenol reagent.J. Biol. Chem., 193, 265–275 (1951).

    PubMed  CAS  Google Scholar 

  • McCann, P. and Pegg, A. E., Ornithine decarboxylase as an enzyme target for therapy.Pharmac Ther., 54, 195–215 (1992).

    Article  CAS  Google Scholar 

  • McCormick, D. L. and Spicer, A. M., Nordihydroguaiaretic acid suppression of rat mammary carcinogenesis induced byN-methyl-N-nitrosourea.Cancer Lett., 37, 139–146 (1987).

    Article  PubMed  CAS  Google Scholar 

  • Mehta, R. G. and Moon, R. C., Characterization of effective chemopreventive agents in mammary glandin vitro using an initiation-promotion protocol.Anticancer Res., 11, 593–596 (1991).

    PubMed  CAS  Google Scholar 

  • Metcalf, B. W., Bey, P., Danzin, C., Jung, M. J., Casara, P. and Vevert, J. P., Catalystic irreversible inhibition of mammalian ornithine decarboxylase by substrate and product analogues.J. Am. Chem. Soc., 100, 2551–2553 (1978).

    Article  CAS  Google Scholar 

  • Nagabhushan, M. and Bhide, S. V., Curcumin as an inhibitor of cancerJ. Am. Coll. Nutr., 11, 192–198 (1992).

    PubMed  CAS  Google Scholar 

  • Nakadate, T., Yamamoto, S., Aizu, E. and Kato, R., Effects of flavonoids and antioxidants on 12-O-tetradecanoylphorbol-13-acetate-caused epidermal ornithine decarboxylase induction and tumor promotion in relation to lipoxygenase inhibition by these components.Gann, 75, 214–222 (1984).

    PubMed  CAS  Google Scholar 

  • Nakadate, T., Yamamoto, S., Iseki, H., Sonoda, S., Takemaru, S., Ura, A., Hosoda, T. and Kato, R., Inhibition of 12-O-tetradecanoylphorbol-13-acetate-induced tumor promotion by nordihydroguaiaretic acid a lipoxygenase inhibitor, andp-bromophenacryl bromide, a phospholipase A2 inhibitor.Gann, 73, 841–843 (1982).

    PubMed  CAS  Google Scholar 

  • OBrien, T. G., Megosh, L. C., Gilliard G. and Soler, A. P., Ornithine decarboxylase overexpression is a sufficient condition for tumor promotion in mouse skin.Cancer Res., 57, 2630–2637 (1997).

    CAS  Google Scholar 

  • Pegg, A. E., Polyamine metabolism and its importance in neoplastic growth and as a target for chemotherapy.Cancer Res., 48, 759–774 (1988).

    PubMed  CAS  Google Scholar 

  • Pegg, A. E. and McCann, P. P., Polyamine metabolism and function: a review.Am. J. Physiol., 243, 212–221 (1982).

    Google Scholar 

  • Peña, A., Reddy, C. D., Wu, S., Hickok, N. J., Reddy, E. P., Yumet, G., Soprano, D. R. and Soprano, K.J., Regulation of human ornithine decarboxylase express-sion by the c-Myc-Max protein complex.J. Biol. Chem., 268, 27277–27285 (1993).

    PubMed  Google Scholar 

  • Pohjanpelto, P., Holtta, E. and Janne, O. A., Mutant strain of Chinese hamster ovary cells with no detectable ornithine decarboxylase activity.Mol. Cell. Biol., 5,

  • Shantz, L. M., Hu, R.-H. and Pegg, A. E., Regulation of ornithine decarboxylase in a transformed cell line that overexpresses translocation initiation factor elF-4E.Cancer Res., 56, 3265–3269 (1996).

    PubMed  CAS  Google Scholar 

  • Sharma, O. P., Antioxidant activity of curcumin and related compounds.Biochem. Pharmacol., 25, 1811–1812 (1976).

    Article  PubMed  CAS  Google Scholar 

  • Sharma, S., Stutzman, J. D., Kelloff, G. J. and Steele, V. E., Screening of potential chemopreventive agents using biochemical markers of carcinogenesis.Cancer Res., 54, 5848–5855 (1994).

    PubMed  CAS  Google Scholar 

  • Smith, W. A. and Gupta, R., Use of a microsome-mediated test system to assess efficacy and mechanisms of cancer chemopreventive agents.Carcinogenesis, 17, 1285–1290 (1996).

    Article  PubMed  CAS  Google Scholar 

  • Srimal, R. C. and Dhawan, B. N., Pharmacology of diferuloylmethane (curcumin), a non-steroidal antiinflammatory agent.J. Pharm. Pharmacol., 25, 447–452 (1973).

    PubMed  CAS  Google Scholar 

  • Strickalnd, J. E., Greenhalgh, D. A., Koceva-Chyla, A., Hennings, H., Restrepo, C., Balaschak, M. and Yuspa, S. H., Development of murine epidermal cell lines which contain an activatedrasHa oncogene and form papillomas in skin grafts on athymic nude mouse hosts.Cancer Res., 48, 165–169 (1988).

    Google Scholar 

  • Szarka, C. E., Grana, G. and Engstrom, P., Chemoprevention of cancer.Curr. Probl. Cancer, 18, 1–78 (1994).

    Article  Google Scholar 

  • Thompson, H. L. and Roman, A. M., Effects of DL-2-di-fluoromethyl-ornithine and endocrine manipulation on their induction of mammary carcinogenesis by MNU.Carcinogenesis, 7, 2003–2006 (1986).

    Article  PubMed  CAS  Google Scholar 

  • Tobias, K. E. and Kahana, C., Intersubunit location of the active site of mammalian ornithine decarboxylase as determine by hybridization of site-directed mutants.Biochemistry, 32, 5842–5847 (1993).

    Article  PubMed  CAS  Google Scholar 

  • van Daalen Wetters, T., Brabant, M. and Collino, P., Regulation of ornithine decarboxylase activity by cell growth, serum and tetradecanoylphorbol acetate is governed primarily by sequences within the coding region of the gene.Nucleic Acids Res., 17, 9843–9860 (1989).

    Article  PubMed  Google Scholar 

  • Verma, A. K. and Boutwell, R. K., Vitamin A acid (retinoic acid), a potent inhibitor of 12-O-tetradecanoylphorbol-13-acetate-induced ornithine decarboxylase activity in mouse epidermis.Cancer Res., 37, 2196–2201 (1977).

    PubMed  CAS  Google Scholar 

  • Verma, A. K., Shapas, B. G., Rice, H. M. and Boutwell, R. K., Correlation of the inhibition by retinoids of tumor promoter-induced mouse epidermal ornithine decarboxylase activity and of skin tumor promotion.Cancer Res., 39, 419–425 (1979).

    PubMed  CAS  Google Scholar 

  • Verma, A. K., Inhibition of tumor promoter 12-O-tetra decanoylphorbol-13-acetate-induced synthesis of epidermal ornithine decarboxylase messenger RNA and diacylglycerol-promoted mouse skin tumor formation by retinoic acid.Cancer Res., 48, 2168–2173 (1988).

    PubMed  CAS  Google Scholar 

  • Wargovich, M. J., Diallyl sulfide, a flavor component of garlic (Allium sativum), inhibits dimethylhydrazine-induced colon cancer.Carcinogenesis, 8, 487–489 (1987).

    Article  PubMed  CAS  Google Scholar 

  • Wargovich, M. J. and Goldberg, M. T., Diallyl sulfide, a naturally occurring thioehter that inhibits carcinogen-induced nuclear damage to colon epithelial cells in vivo.Mutat. Res., 143, 127–129 (1985).

    PubMed  CAS  Google Scholar 

  • Wei, H., Tye, L., Brensnick, E. and Birt, D. F., Inhibitory effect of apigenin, a plant flavonoid, on epidermal ornithine decarboxylase and skin tumor promotion in mice.Cancer Res., 50, 499–502 (1990).

    PubMed  CAS  Google Scholar 

  • Williams-Ashman, H. G. and Canellakis, Z. N., Polyamines in mammalian biology and medicine.Perspect. Biol. Med., 22, 421–453 (1979).

    PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Sang Kook Lee.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Lee, S.K., Pezzuto, J.M. Evaluation of the potential of cancer chemopreventive activity mediated by inhibition of 12-O-tetradecanoyl phorbol 13-acetate-induced ornithine decarboxylase activity. Arch Pharm Res 22, 559–564 (1999). https://doi.org/10.1007/BF02975326

Download citation

  • Received:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF02975326

Key words

Navigation