Antitumor-Promoting Activities of Tannic Acid, Ellagic Acid, and Several Gallic Acid Derivatives in Mouse Skin

  • Jean-Pierre Perchellet
  • Hala U. Gali
  • Elisabeth M. Perchellet
  • Darren S. Klish
  • Andrew D. Armbrust
Part of the Basic Life Sciences book series (BLSC, volume 59)

Abstract

Naturally occurring plant phenols with antimutagenic and anticarcinogenic activities were tested for their abilities to inhibit the biochemical and biological effects of the potent tumor promoter 12- O-tetradecanoylphorbol-13-acetate (TPA) in mouse epidermis in vivo. When applied topically to mouse skin, tannic acid (TA), ellagic acid, and several gallic acid derivatives all inhibit TPA-induced ornithine decarboxylase activity, hydroperoxide production, and DNA synthesis, three biochemical markers of skin tumor promotion. Moreover, in the two-step initiation-promotion protocol, the same phenolic compounds also inhibit the incidence and yield of skin tumors promoted by TPA. TA is the most effective of these treatments. Since they are already known to inhibit tumor initiation, the plant phenols protecting against skin tumor promotion by TPA may be universal inhibitors of multistage carcinogenesis. TA and other polyphenols, therefore, might be valuable in cancer therapy and/or prevention.

Keywords

Selenium Flavonoid Gall Alkaloid Hydroperoxide 

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    Slaga, T.J. Multistage skin tumor promotion and specificity of inhibition. In: Slaga, T.J. (ed.)Mechanisms of tumor promotion, Vol.2.CRC Press, Boca Raton, pp.189-196 (1984).Google Scholar
  2. 2.
    Perchellet, J.P.; Perchellet, E.M. Phorbol ester tumor promoters and multistage skin carcinogenesis. ISI Atlas of Science: Pharmacol. 2:325 (1988).Google Scholar
  3. 3.
    Kawamura, H.; Strickland, J.E.; Yuspa, S.H. Association of resistance to terminal differentiation with initiation of carcinogenesis in adult mouse epidermal cells. Cancer Res. 45:2748 (1985).PubMedGoogle Scholar
  4. 4.
    Hennings, H.; Yuspa, S.H. Two-stage tumor promotion in mouse skin: an alternative interpretation. J. Natl. Cancer Inst. 74:735 (1985).PubMedGoogle Scholar
  5. 5.
    Zee-Cheng, R.K.Y.; Cheng, C.C. Ellagic acid. Drugs of the Future 11:1029 (1986).Google Scholar
  6. 6.
    Hayatsu, H.; Arimoto, S.; Negishi, T. Dietary inhibitors of mutagenesis and carcinogenesis. Mutat. Res. 202:429 (1988).PubMedCrossRefGoogle Scholar
  7. 7.
    Perchellet, J.P.; Perchellet, E.M. Antioxidants and multistage carcinogenesis in mouse skin. Free Radical Biol. Med. 7:377 (1989).CrossRefGoogle Scholar
  8. 8.
    Boone, C.W.; Kelloff, G.J.; Malone, W.E. Identification of candidate cancer chemopreventive agents and their evaluation in animal models and human clinical trials: a review. Cancer Res. 50:2 (1990).PubMedGoogle Scholar
  9. 9.
    Das, M.; Mukhtar, H.; Bik, D.P.; Bickers, D.R. Inhibition of epidermal xenobiotic metabolism in SENCAR mice by naturally occurring plant phenols. Cancer Res. 47:760 (1987).PubMedGoogle Scholar
  10. 10.
    Das, M.; Khan, W.A.; Asokan, P.; Bickers, D.R.; Mukhtar, H. Inhibition of polycyclic hydrocarbon-DNA adduct formation in epidermis and lungs of SENCAR mice by naturally occurring plant phenols. Cancer Res. 47:767 (1987).PubMedGoogle Scholar
  11. 11.
    Mukhtar, H.; Das, M.; Khan, W.A.; Wang, Z.Y.; Bik, D.P.; Bickers, D.R. Exceptional activity of tannic acid among naturally occurring plant phenols in protecting against 7,12-dimethylbenz[a]anthracene-, benzo[a]pyrene-, 3-methylcholanthrene-, and N-methyl-N-nitrosourea-induced skin tumorigenesis in mice. Cancer Res. 48:2361 (1988).PubMedGoogle Scholar
  12. 12.
    Athar, M.; Khan, W.A.; Mukhtar, H. Effect of dietary tannic acid on epidermal, lung, and forestomach polycyclic aromatic hydrocarbon metabolism and tumorigenicity in Sencar mice. Cancer Res. 49:5784 (1989).PubMedGoogle Scholar
  13. 13.
    Lesca, P. Protective effects of ellagic acid and other plant phenols on benzo[a]pyrene-induced neoplasia in mice. Carcinogenesis 4:1651 (1983).PubMedCrossRefGoogle Scholar
  14. 14.
    Mukhtar, H.; Das, M.; Del Tito, B.J.; Bickers, D.R. Protection against 3-methylcholanthreneinduced skin tumorigenesis in BALB/c mice by ellagic acid. Biochem.Biofhys.Res. Commun. 119:751 (1984).CrossRefGoogle Scholar
  15. 15.
    Mukhtar, H.; Del Tito, B.J.; Marcelo, C.L.; Das, M.; Bickers, D.R. Ellagic acid: a potent naturally occurring inhibitor of benzo[a]pyrene metabolism and its subsequent glucuronidation, sulfation and covalent binding to DNA in cultured BALB/c mouse keratinocytes. Carcinogenesis 5:1565 (1984).PubMedCrossRefGoogle Scholar
  16. 16.
    Chang, R.L.; Huang, M.T.; Wood, A.W.; Wong, C.Q.; Newmark, H.L.; Yagi, H.; Sayer, J.M.; Jerina, D.M.; Conney, A.H. Effects of ellagic acid and hydroxylated flavonoids on the tumorigenicity of benzo[a]pyrene and (±)-7β3,8α-dihydroxy-9α,10α-epoxy, 7,8,9,10-tetrahydrobenzo[a]pyrene on mouse skin and in the newborn mouse. Carcinogenesis 6:1127 (1985).PubMedCrossRefGoogle Scholar
  17. 17.
    Mukhtar, H.; Das, M.; Bickers, D.R. Inhibition of 3-methylcholanthrene-induced skin tumorigenicity in BALB/c mice by chronic oral feeding of trace amounts of ellagic acid in drinking water. Cancer Res. 46:2262 (1986).PubMedGoogle Scholar
  18. 18.
    Del Tito, B.J.; Mukhtar, H.; Bickers, D.R. Inhibition of epidermal metabolism and DNA-binding of benzo[a]pyrene by ellagic acid. Biochem.Biophys.Res.Commun. 114:388 (1984).CrossRefGoogle Scholar
  19. 19.
    Teel, R.W.; Martin, R.M.; Allahyari, R. Ellagic acid metabolism and binding to DNA in organ expiant cultures of the rat. Cancer Lett. 36:203 (1987).PubMedCrossRefGoogle Scholar
  20. 20.
    Wood, A.W.; Huang, M.T.; Chang, R.L.; Newmark, H.L.; Lehr, R.E.; Yagi, H.; Sayer, J.M.; Jerina, D.M.; Conney, A.H. Inhibition of the mutagenicity of bay-region diol epoxides of polycyclic aromatic hydrocarbons by naturally occurring plant phenols: exceptional activity of ellagic acid. Proc. Natl. Acad. Sci. 79:5513(1982).PubMedCrossRefGoogle Scholar
  21. 21.
    Blumberg, P.M. Protein kinase C as the receptor for the phorbol ester tumor promoters: sixth Rhodes memorial award lecture. Cancer Res. 48:1 (1988).PubMedGoogle Scholar
  22. 22.
    Wirth, P.J.; Yuspa, S.H.; Thorgeirsson, S.S.; Hennings, H. Induction of common patterns of polypeptide synthesis and phosphorylation by calcium and 12-0-tetradecanoylphorbol-13-acetate in mouse epidermal cell culture. Cancer Res. 47:2831 (1987).PubMedGoogle Scholar
  23. 23.
    Verma, A.K.; Pong, R.C.; Erickson, D. Involvement of protein kinase C activation in ornithinedecarboxylase gene expression in primary culture of newborn mouse epidermal cells and skin tumor promotion by 12-0-tetradecanoylphorbol-13-acetate. Cancer Res. 46:6149 (1986).PubMedGoogle Scholar
  24. 24.
    O’Brien, T.G. The induction of ornithine decarboxylase as an early, possibly obligatory, event in mouse skin carcinogenesis. Cancer Res. 36:2644 (1976).PubMedGoogle Scholar
  25. 25.
    Perchellet, E.M.; Abney, N.L.; Perchellet, J.P. Stimulation of hydroperoxide generation in mouse skins treated with tumor-promoting or carcinogenic agents in vivo and in vitro. Cancer Lett. 42:169 (1988).PubMedCrossRefGoogle Scholar
  26. 26.
    Perdiellet, E.M.; Perchellet, J.P. Characterization of the hydroperoxide response observed in mouse skin treated with tumor promoters in vivo. Cancer Res. 49:6193 (1989).Google Scholar
  27. 27.
    Paulsen, J.E.; Astrup, E.G. Effects of single applications of 12-0-tetradecanoylphorbol-13-acetate, mezerein, or ethylphenylpropiolate on DNA synthesis and polyamine levels in hairless mouse epidermis. Cancer Res. 43:4126 (1983).PubMedGoogle Scholar
  28. 28.
    Perchellet, E.M.; Jones, D.; Perchellet, J.P. Ability of the Ca2+ ionophores A23187 and ion-omycin to mimic some of the effects of the tumor promoter 12-0-tetradecanoylphorbol-13-acetate on hydroperoxide production, ornithine decarboxylase activity, and DNA synthesis in mouse epidermis in vivo. Cancer Res. 50:5806 (1990).PubMedGoogle Scholar
  29. 29.
    Perchellet, J.P.; Boutwell, R.K. Effects of 3-isobutyl-l-methylxanthine and cyclic nucleotides on 12-0-tetradecanoylphorbol-13-acetate-induced ornithine decarboxylase activity in mouse epidermis in vivo. Cancer Res. 41:3918 (1981).PubMedGoogle Scholar
  30. 30.
    Takigawa, M.; Simsiman, R.C.; Boutwell, R.K. The difference between the effects of single and double applications of 12-0-tetradecanoyl-phorbol-13-acetate, a potent tumor promoter, on polyamine metabolism and nucleic acid synthesis in mouse epidermis. Carcinogenesis 4:5 (1983).PubMedCrossRefGoogle Scholar
  31. 31.
    Perchellet, J.P.; Abney, N.L.; Thomas, R.M.; Guislain, Y.L.; Perchellet, E.M. Effects of combined treatments with selenium, glutathione, and vitamin E on glutathione peroxidase activity, ornithine decarboxylase induction, and complete and multistage carcinogenesis in mouse skin. Cancer Res. 47:477 (1987).PubMedGoogle Scholar
  32. 32.
    Perchellet, J.P.; Abney, N.L.; Thomas, R.M.; Perchellet, E.M.; Maatta, E.A. Inhibition of multistage tumor promotion in mouse skin by diethyldithiocarbamate. Cancer Res. 47:6302 (1987).PubMedGoogle Scholar
  33. 33.
    Smart, R.C.; Huang, M-T.; Conney, A.H. sn-l,2-Diacylglycerols mimic the effects of 12-0-tetradecanoylphorbol-13-acetate in vivo by inducing biochemical changes associated with tumor promotion in mouse epidermis. Carcinogenesis 7:1865 (1986).PubMedCrossRefGoogle Scholar
  34. 34.
    DiGiovanni, J.; Decina, P.C.; Pritchett, W.P.; Cantor, J.; Aalfs, K.K.; Coombs, M.M. Mechanism of skin tumor promotion by chrysarobin. Cancer Res. 45:2584 (1985).PubMedGoogle Scholar
  35. 35.
    Kruszewski, F.H.; Chenicek, K.J.; DiGiovanni, J. Effect of application frequency on epidermal ornithine decarboxylase induction by chrysarobin in SENCAR mice. Cancer Lett. 32:263 (1986).PubMedCrossRefGoogle Scholar
  36. 36.
    Kruszewski, F.H.; DiGiovanni, J. Alterations in epidermal polyamine levels and DNA synthesis following topical treatment with chrysarobin in SENCAR mice. Cancer Res. 48:6390 (1988).PubMedGoogle Scholar
  37. 37.
    Baxter, C.S.; Miller, M.L. Mechanism of mouse skin tumor promotion by n-dodecane. Carcinogenesis 8:1787 (1987).PubMedCrossRefGoogle Scholar
  38. 38.
    Fujiki, H.; Suganuma, M.; Nakayasu, M.; Tahira, T.; Endo, Y.; Shudo, K.; Sugimura, T. Structure-activity studies on synthetic analogues (indolactams) of the tumor promoter teleocidin. Gann 75:866 (1984).PubMedGoogle Scholar
  39. 39.
    Takigawa, M.; Verma, A.K.; Simsiman, R.C.; Boutwell, R.K. Inhibition of mouse skin tumor promotion and of promoter-stimulated epidermal polyamine biosynthesis by α-difluoromethylornithine. Cancer Res. 43:3732 (1983).PubMedGoogle Scholar
  40. 40.
    Muhtasib, H.U.; Perchellet, E.M.; Perchellet, J.P. Tannic acid inhibition of phorbol esterinduced ornithine decarboxylase activity in mouse epidermis in vivo. Proc. Am. Assoc. Cancer. Res. 32:151 (1991).Google Scholar
  41. 41.
    Gali, H.U.; Perchellet, E.M.; Perchellet, J.P. Inhibition of tumor promoter-induced ornithine decarboxylase activity by tannic acid and other polyphenols in mouse epidermis in vivo. Cancer Res. 51:2820 (1991).PubMedGoogle Scholar
  42. 42.
    Gilmour, S.K.; Avdalovic, N.; Madara, T.; O’Brien, T.G. Induction of ornithine decarboxylase by 12-0-tetradecanoylphorbol-13-acetate in hamster fibroblasts. I. Relationship between levels of enzyme activity, immunoreactive protein and RNA during the induction process. J. Biol. Chem. 260:16439 (1985).PubMedGoogle Scholar
  43. 43.
    Yoshizawa, S.; Horiuchi, T.; Fujiki, H.; Yoshida, T.; Okuda, T.; Sugimura, T. Antitumor promoting activity of (-)-epigallocatechin gallate, the main constituent of “tannin” in green tea. Phytother. Res. 1:44 (1987).CrossRefGoogle Scholar
  44. 44.
    Gschwendt, M.; Hecker, E. On the active principles of the spurge family. II. Skin irritant and cocarcinogenic factors from Euphorbia triangularis Desf. Z. Krehsforsch. 81:193(1974).CrossRefGoogle Scholar
  45. 45.
    Verma, A.K. The protein kinase C activator L-α-dioctanoylglycerol: a potent stage II mouse skin tumor promoter. Cancer Res. 48:1736 (1988).PubMedGoogle Scholar
  46. 46.
    Fujiki, H.; Suganuma, M.; Ninomiya, M.; Yoshizawa, S.; Yamashita, K.; Takayama, S.; Hitotsuyanagi, Y.; Sakai, S.; Shudo, K.; Sugimura, T. Similar, potent tumor-promoting activity of all isomers of teleocidins A and B in a two-stage cardnogenesis experiment on the skin of CD-I mice. Cancer Res. 48:4211 (1988).PubMedGoogle Scholar
  47. 47.
    Slaga, T.J.; Klein-Szanto, A.J.P.; Triplett, L.L.; Yotti, L.P.; Trosko, J.E. Skin tumor-promoting activity of benzoyl peroxide, a widely used free radical-generating compound. Science 213:1023 (1981).PubMedCrossRefGoogle Scholar
  48. 48.
    O’Connell, J.F.; Klein-Szanto, A.J.P.; DiGiovanni, D.M.; Fries, J.W.; Slaga, T.J. Enhanced malignant progression of mouse skin tumors by the free-radical generator benzoyl peroxide. Cancer Res. 46:2863 (1986).PubMedGoogle Scholar
  49. 49.
    Pence, B.C.; Reiners, J.J. Murine epidermal xanthine oxidase activity: correlation with degree of hyperplasia induced by tumor promoters. Cancer Res. 47:6388 (1987).PubMedGoogle Scholar
  50. 50.
    Donnelly, T.E.; Pelling, J.C.; Anderson, CL.; Dalbey, D. Benzoyl peroxide activation of protein kinase C activity in epidermal cell membrane. Carcinogenesis 8:1871 (1987).PubMedCrossRefGoogle Scholar
  51. 51.
    Miller, M.L.; Andringa, A.; Baxter, C.S. Critical comparison of histological and morphometric changes in SENCAR mouse epidermis in response to n-dodecane, 12-0-tetradecanoylphorbol-13-acetate and mezerein. Cardnogenesis 9:1959 (1988).CrossRefGoogle Scholar
  52. 52.
    Cerutti, P.A. Prooxidant states and tumor promotion. Science 227:375 (1985).PubMedCrossRefGoogle Scholar
  53. 53.
    Kensler, T.W.; Taffe, B.G. Free radicals in tumor promotion. Adv. Free Radical Biol. Med. 2:347 (1986).CrossRefGoogle Scholar
  54. 54.
    Hartley, J.A.; Gibson, N.W.; Kilkenny, A.; Yuspa, S.H. Mouse keratinocytes derived from initiated skin or papillomas are resistant to DNA strand breakage by benzoyl peroxide: a possible mechanism for tumor promotion mediated by benzoyl peroxide. Carcinogenesis 8:1827 (1987).PubMedCrossRefGoogle Scholar
  55. 55.
    Speier, C; Baker, S.S.; Newburger, P.E. Relationships between in vitro selenium supply, glutathione peroxidase activity, and phagocytic function in the HL-60 human myeloid cell line. J. Biol. Chem. 260:8951 (1985).PubMedGoogle Scholar
  56. 56.
    Baird, W.M.; Sedgwick, J.A.; Boutwell, R.K. Effects of phorbol and four diesters of phorbol on the incorporation of tritiated precursors into DNA, RNA, and protein in mouse epidermis. Cancer Res. 31:1434 (1971).PubMedGoogle Scholar
  57. 57.
    Kinzel, V.; Loehrke, H.; Goerttler, K.; Fürstenberger, G.; Marks, F. Suppression of the first stage of phorbol 12-tetradecanoate-13-acetate-effected tumor promotion in mouse skin by nontoxic inhibition of DNA synthesis. Proc. Natl. Acad. Sci. USA 81:5858 (1984).PubMedCrossRefGoogle Scholar
  58. 58.
    Burton, K. A study of the conditions and mechanisms of the diphenylamine reaction for the colorimetric estimation of deoxyribonucleic acid. Biochem. J. 62:315 (1956).PubMedGoogle Scholar
  59. 59.
    Aldaz, CM.; Conti, C.J.; Gimenez, I.B.; Slaga, T.J.; Klein-Szanto, A.J.P. Cutaneous changes during prolonged application of 12-0-tetradecanoylphorbol-13-acetate on mouse skin and residual effects after cessation of treatment. Cancer Res. 45:2753 (1985).PubMedGoogle Scholar

Copyright information

© Springer Science+Business Media New York 1992

Authors and Affiliations

  • Jean-Pierre Perchellet
    • 1
  • Hala U. Gali
    • 1
  • Elisabeth M. Perchellet
    • 1
  • Darren S. Klish
    • 1
  • Andrew D. Armbrust
    • 1
  1. 1.Anti-Cancer Drug LaboratoryKansas State UniversityManhattanUSA

Personalised recommendations