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Cepharanthine inhibits two-stage tumor promotion by 12-O-tetradecanoylphorbol 13-acetate and mezerein on skin tumor formation in mice initiated with 7,12-dimethylbenz[a]anthracene

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  • Experimental Oncology
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Summary

Cepharanthine, isolated fromStephania cepharantha, is one of the bisbenzylisoquinoline-type alka-loids. We have found that it inhibits tumor promotion after topical application in two-stage carcinogenesis in mouse skin. Epidermal ornithine decarboxylase activities inhibited by topical application of cepharanthine, with an 5 Μg/mouse) and mezerein (5 Μg/mouse) were found to be inhibited by topical application of cepharanthine, with a ED50 of 1.2 Μmol and 1.4 Μmol respectively. These inhibitory effects of cepharanthine are considered to be related to its antitumor activity in two-stage carcinogenesis in mouse skin. Cell-mediated immunosuppression by TPA was unaffected by topical application of cepharanthine. A diet containing 0.005% cepharanthine (about 0.5 mg mouse day) slightly suppressed the two-stage promotion of skin tumors by twice-weekly applications of 2.5 Μg TPA for 2 weeks (first stage) followed by twice-weekly applications of 2.5 Μg mezerein for 23 weeks (second stage) in ICR mice following initiation by 50 Μg 7,12-dimethylbenz[a]anthracene. Oral administration of cepharanthine inhibits the tumor promotion in two-stage carcinogenesis in mouse skin.

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Abbreviations

DMBA:

7,12-dimethylbenz[a]anthracene

DTH:

delayed-type hypersensitivity

ODC:

ornithine decarboxylase

TPA:

12-O-tetradecanoylphorbol 13-acetate

References

  • Blumberg PM (1981) In vitro studies on the mode of action of the phorbol ester potent tumor promoters. CRC Crit Rev Toxicol 9:199–234

    Google Scholar 

  • Compton SJ, Jones CG (1985) Mechanism of dye response and interference in the Bradford protein assay. Anal Biochem 151:369–374

    Google Scholar 

  • Diamond L, O'Brien TG, Baird WM (1980) Tumor promoters and the mechanism of tumor promotion. Adv Cancer Res 32:1–74

    Google Scholar 

  • Goto K, Tanaka R (1984) Cepharanthine protection of Na+, Ca2+-activated adenosine triphosphatase of plasma membranes from rat cerebral synaptosomes against inhibition by ascorbate. Biochem Pharmacol 33:3912–3914

    Google Scholar 

  • Hasegawa S (1949) Studies on the chemotherapy of tuberculosis. Jpn J Exp Med 20:69–101

    Google Scholar 

  • Hasegawa S, Shinozuka T (1950) The effect of cepharanthin in the prevention of tuberculosis. Jpn J Exp Med 20:541–557

    Google Scholar 

  • Hasegawa S, Takahashi K (1949) The effect of cepharanthin on pertussis. Jpn J Exp Med 20:229–234

    Google Scholar 

  • Hashimoto T, Adachi S, Sato M, Hasegawa S (1950) The cepharanthin treatment of leprosy. Jpn J Exp Med 20:461–472

    Google Scholar 

  • Kondo H, Keimatu I (1938)Sinomenium andCocculus alkaloids: XLVIII. Constitution of cepharanthine. J Pharm Soc Jpn 58:906–919

    Google Scholar 

  • Miyahara M, Aono K, Queseda JS, Shimono K, Baba Y, Yamashita S (1978) Protection by cepharanthine of the mitochondrial function from damage induced by snake venom, phospholipase A2, lysolecithin and lead. Cell Struct Funct 3:61–65

    Google Scholar 

  • Muller HK, Halliday GM, Knight BA (1985) Carcinogen-induced depletion of cutaneous Langerhans' cells. Br. J Cancer 52:81–85

    Google Scholar 

  • Nakadate T, Yamamoto S, Ishii M, Kato R (1982a) Inhibition of 12-O-tetradecanoylphorbol-13-acetate-induced epidermal ornithine decarboxylase activity by phospholipase A2 inhibitors and lipoxygenase inhibitor. Cancer Res 42:2841–2845

    Google Scholar 

  • Nakadate T, Yamamoto S, Ishii M, Kato R (1982b) Inhibition of 12-O-tetradecanoylphorbol-13-acetate-induced epidermal ornithine decarboxylase activity by lipoxygenase inhibitors: possible role of product(s) of lipoxygenase pathway. Carcinogenesis 3:1411–1414

    Google Scholar 

  • Nakagawa S, Kanazawa K, Hirota R, Ishizuka K, Kashiwazaki K, Tanaka M, Sato K (1989) Experimental papilloma development on murine skin and protein kinase C; effect of topical cepharan-thine application. J Nihon Univ Med Assoc 48:868–874

    Google Scholar 

  • Nihashi Y, Koga Y, Gondo H, Taniguchi K, Nomoto K (1985) Thymus-dependent increase in number of T cells in parathymic lymph nodes induced by the biscoclaurine alkaloid, cepharanthine. Immunobiology 170:351–364

    Google Scholar 

  • O'Brien TG, Simsimann RC, Boutwell RK (1975) Induction of polyamine-biosynthetic enzymes in mouse epidermis by tumorpromoting agents. Cancer Res 35:1662–1670

    Google Scholar 

  • Slaga TJ, Fischer SM, Weeks CE, Nelson K, Mamrack M, Klein-Szanto AJP (1982) Specificity and mechanism(s) of promoter inhibitors in multistage promotion. In: Hecker E, Fusenig NE, Kunz W, Marks F, Thielmann HW (eds) Carcinogenesis, vol 7. Raven, New York, pp 19–34

    Google Scholar 

  • Takeuchi M, Fujiki H, Nitta K (1986) Cell-mediated immune response in mice during the two-stage carcinogenesis experiment by 7,12-dimethylbenz[a]anthracene and 12-O-tetradecanoyl-phorbol-13-acetate. Jpn J Exp Med 56:131–134

    Google Scholar 

  • Takeuchi T, Sato S (1985) Effect of cepharanthine on cell-type conversion in B16 mouse melanoma cells. J Dermatol 12:138–142

    Google Scholar 

  • Tamaki K, Fujiwara H, Katz SI (1981) The role of epidermal cells in the induction and suppression of contact sensitivity. J Invest Dermatol 76:275–278

    Google Scholar 

  • Verma AK, Rice HM, Boutwell RK (1977) Prostaglandins and skin tumor promotion: inhibition of tumor promoter-induced ornithine decarboxylase activity in epidermis by inhibitors of prostaglandin synthesis. Biochem Biophys Res Commun 79:1160–1166

    Google Scholar 

  • Verma AK, Ashendel CL, Boutwell RK (1980) Inhibition by prostaglandin synthesis inhibitors of the induction of epidermal ornithine decarboxylase activity, the accumulation of prostaglandins, and tumor promotioin caused by 12-O-tetradecanoylphorbol-13-acetate. Cancer Res 40:308–315

    Google Scholar 

  • Yasukawa K, Takido M, Takeuchi M, Akasu M, Nakagawa S (1989) Inhibitory effect of cepharanthine and its related compounds on 12-O-tetradecanoylphorbol-13-acetate-induced inflammation and inhibition of tumor promotion by cepharanthine in two-stage carcinogenesis in mice. Nihon Univ J Med 31:229–234

    Google Scholar 

  • Yasukawa K, Takido M, Takeuchi M, Akasu M, Nakagawa SS (1990) Inhibitory effects of flavonol glycosides on 12-O-tetradecanoylphorbol-13-acetate-induced tumor promotion. Chem Pharm Bull (Tokyo) 38:774–776

    Google Scholar 

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Yasukawa, K., Takido, M., Takeuchi, M. et al. Cepharanthine inhibits two-stage tumor promotion by 12-O-tetradecanoylphorbol 13-acetate and mezerein on skin tumor formation in mice initiated with 7,12-dimethylbenz[a]anthracene. J Cancer Res Clin Oncol 117, 421–424 (1991). https://doi.org/10.1007/BF01612761

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  • DOI: https://doi.org/10.1007/BF01612761

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