Abstract
Modifying effects of a fungal product, flavoglaucin, and four plant‐derived chemicals, shikonin, gingerol, oleanolic acid and paeoniflorin, on intestinal carcinogenesis were examined in a rat model using azoxymethane (AOM). A total of 280 male F344 rats, 6 weeks old, were divided into 12 groups. Group 1 (30 rats) was given two subcutaneous injections of 15 mg/kg of AOM at the start of the experiment. Groups 2 (30 rats), 3 (20 rats), 4 (20 rats), 5 (30 rats) and 6 (30 rats) received a test chemical (flavoglaucin, shikonin, gingerol, oleanolic acid or paeoniflorin, respectively) in the diet at a concentration of 0.02% for 3 weeks, during which time AOM was applied, and then kept on basal diet until the end of experiment (one year). Groups 7–11 (each 20 rats) were given a test chemical corresponding to Groups 2–6, respectively. Group 12 (20 rats) served as a control. The incidence and average number of intestinal tumors in Group 2 (47%, 0.57 ± 0.68) were significantly less than in Group 1 (74%, 1.07 ± 0.87) (P < 0.05, respectively). Multiplicity of intestinal neoplasms of Group 3 (0.55 ± 0.60) or 4 (0.47 ± 0.51) was also significantly smaller than that of Group 1 (P < 0.05 and P < 0.01, respectively). These results suggest that flavoglaucin, shikonin and gingerol might be promising chemopreventive agents for intestinal neoplasia.
Keywords: Chemoprevention, Fungal metabolite, Herb, Intestinal carcinogenesis, Blocking effect
Full Text
The Full Text of this article is available as a PDF (307.4 KB).
REFERENCES
- 1. ) Sporn , M. B. and Newton , D. L.Chemoprevention of cancer with retinoids . Fed. Proc , 38 , 2528 – 2534 ( 1979. ). [PubMed] [Google Scholar]
- 2. ) Wattenberg , L. W.Chemoprevention of cancer . Cancer Res , 45 , 1 – 8 ( 1985. ). [PubMed] [Google Scholar]
- 3. ) Weinstein , I. B.Cancer prevention: recent progress and future opportunities . Cancer Res. , 51 , 5080s – 5085s ( 1991. ). [PubMed] [Google Scholar]
- 4. ) Tanaka , T.Cancer chemoprevention . Cancer J. , 5 , 11 – 16 ( 1992. ). [Google Scholar]
- 5. ) Cullen , J. W.The National Cancer Institute's intervention trials . Cancer , 62 , 1851 – 1864 ( 1988. ). [DOI] [PubMed] [Google Scholar]
- 6. ) Reddy , S. , Mori , H. and Nicolais , M.Effect of dietary wheat bran and dehydrated citrus fiber on azoxymethane‐induced intestinal carcinogenesis in Fischer 344 rats . J. Natl. Cancer Inst , 66 , 553 – 557 ( 1981. ). [PubMed] [Google Scholar]
- 7. ) Narisawa , T. , Sato , A. , Tani , M. , Kudo , T. and Takahashi , T.Inhibition of development of methylnitrosourea‐induced rat colon tumors by indomethacin treatment . Cancer Res. , 41 , 1954 – 1957 ( 1981. ). [PubMed] [Google Scholar]
- 8. ) Mori , H. , Tanaka , T. , Shima , H. , Kuniyasu , T. and Takahashi , M.Inhibitory effect of chlorogenic acid on methylazoxymethanol acetate‐induced carcinogenesis in large intestine and liver of hamsters . Cancer Lett , 30 , 49 – 54 ( 1986. ). [DOI] [PubMed] [Google Scholar]
- 9. ) Reddy , B. S. , Sugie , S. , Maruyama , H. , El‐Bayoumy , K. and Marra , P.Chemoprevention of colon carcinogenesis by dietary organoselenium, benzylselenium, benzylseleno‐cyanate, in F344 rats . Cancer Res. , 47 , 5901 – 5904 ( 1987. ). [PubMed] [Google Scholar]
- 10. ) Reddy , B. S. and Sugie , S.Effect of different levels of Omega‐3 and Omega‐6 fatty acids on azoxymethane‐induced colon carcinogenesis in F344 rats . Cancer Res. , 48 , 6642 – 6647 ( 1988. ). [PubMed] [Google Scholar]
- 11. ) Tanaka , T. , Shinoda , T. , Yoshimi , N. , Niwa , K. , Iwata , H.and Mori, H. Inhibitory effect of magnesium hydroxide on methylazoxymethanol acetate‐induced large bowel carcinogenesis in male F344 rats . Carcinogenesis , 10 , 613 – 616 ( 1989. ). [DOI] [PubMed] [Google Scholar]
- 12. ) Wattenberg , L. W. and Fiala , E. S.Inhibition of dimethylhydrazine‐induced neoplasia of the large intestine by carbon disulfide . J. Natl. Cancer Inst. , 60 , 1515 – 1517 ( 1978. ). [DOI] [PubMed] [Google Scholar]
- 13. ) Konoshima , T. , Kozuka , M. , Koyama , J. , Okatani , T. , Tagahara , K. and Tokuda , H.Studies on inhibitors of skin tumor promotion, VI. Inhibitory effects of quinones on Epstein‐Barr virus activation . J. Nat. Prod. , 52 , 987 – 995 ( 1989. ). [DOI] [PubMed] [Google Scholar]
- 14. ) Koshimizu , K. , Ohigashi , H. , Tokuda , H. , Kondo , A. and Yamaguchi , K.Screening of edible plants against possible anti‐tumor promoting activity . Cancer Lett. , 39 , 247 – 257 ( 1988. ). [DOI] [PubMed] [Google Scholar]
- 15. ) Kawai , K. , Mori , H. and Kitamura , J.The uncoupling effect of flavoglaucin, a quinol pigment from Aspergillus chevalieri (MANGIN), on mitochondrial respiration . Toxicol. Lett. , 19 , 321 – 325 ( 1983. ). [DOI] [PubMed] [Google Scholar]
- 16. ) Yamahara , J. , Mochizuki , M. , Rong , H. Q. , Matsuda , H. and Fujimura , H.The anti‐ulcer effect in rats of ginger constituents . J. EthnopharmacoL , 23 , 299 – 304 ( 1988. ). [DOI] [PubMed] [Google Scholar]
- 17. ) Ward , J. M.Morphogenesis of chemically induced neoplasms of the colon and small intestine in rats . Lab. Invest. , 30 , 505 – 513 ( 1974. ). [PubMed] [Google Scholar]
- 18. ) Turner , W. B. “ Fungal Metabolites ,” pp. 141 ( 1971. ). Academic Press Inc. , London and New York . [Google Scholar]
- 19. ) Honda , G. , Sakakibara , F. , Yazaki , K. and Tabata , M.Isolation of deoxyshikonin, antidermatophytic principle from Lithspermum erythrorhizon cell cultures . J, Nat. Prod. , 51 , 152 – 154 ( 1988. ). [DOI] [PubMed] [Google Scholar]
- 20. ) Tanaka , S. , Tajima , M. , Tsukada , M. and Tabata , M. Acomparative study on anti‐inflammatory activities of the enantiomers, shikonin and alkanin . J. Nat. Prod. , 49 , 466 – 469 ( 1986. ). [DOI] [PubMed] [Google Scholar]
- 21. ) Nagabhushan , M. , Amonkar , A. J. and Bhide , S. V.Mutagenicity of gingerol and shogaol and antimutagen‐icity of zingerone in Salmonella/microsome assay . Cancer Lett. , 36 , 221 – 233 ( 1987. ). [DOI] [PubMed] [Google Scholar]
- 22. ) Nakamura , H. and Yamamoto , T.The active part of the [6]‐gingerol molecule in mutagenesis . Mutat. Res. , 122 , 87 – 94 ( 1983. ). [DOI] [PubMed] [Google Scholar]
- 23. ) Ishikawa , Y. , Morimoto , K. and Hamasaki , T.Flavoglaucin, a metabolite of Eurotium chevalieri, its antioxidation and synergism with tocopherol . JAOCS, J. Am. Oil Chem. Soc , 61 , 1864 – 1868 ( 1984. ). [Google Scholar]
- 24. ) Osawa , T. , Namiki , M. and Kawakishi , S.Role of dietary antioxidants in protection against oxidative damage . In “ Antimutagenesis and Anticarcinogenesis Mechanisms II ,” ed. Kuroda Y. , Shankel D. M. and Waters M. D. . pp. 139 – 153 ( 1990. ). Plenum Press; , New York . [DOI] [PubMed] [Google Scholar]
- 25. ) Fiala , E. S. , Kulakis , C. , Christiansen , G. and Weisburger , J. H.In vivo and in vitro metabolism of the colon carcinogen azoxymethane (AOM) . Proc. Am. Assoc. Cancer Res. , 18 , 105 ( 1977. ). [PubMed] [Google Scholar]
- 26. ) Zedeck , M. S.Hydrazine derivatives, azo and azoxy compounds, and methylazoxymethanol and cycasin . In “ Chemical Carcinogens (Vol. 2) ,” ed. Searle C. E. . pp. 915 – 944 ( 1984. ). ACS; , Washington , DC . [Google Scholar]
- 27. ) Fujita , Y. , Yamane , T. , Tanaka , M. , Kuwata , K. , Okuzumi , J. , Takahashi , T. , Fujiki , H. and Okuda , T.Inhibitory effect of (‐)‐epigallocatechin gallate on carcinogenesis with N‐ethyl‐N'‐nitro‐N‐nitrosoguanidine in mouse duodenum . Jpn. J. Cancer Res. , 80 , 503 – 505 ( 1989. ). [DOI] [PMC free article] [PubMed] [Google Scholar]
- 28. ) Ohigashi , H. , Takamura , H. , Koshimizu , K. , Tokuda , H. and Ito , Y.Search for possible antitumor promoters by inhibition of 12‐O‐tetradecanoylphorbol‐13‐acetate‐in‐duced Epstein‐Barr virus activation: ursolic acid and oleanolic acid from an anti‐inflammatory Chinese medicinal plant, Glechoma hederaceae L . Cancer Lett , 30 , 143 – 151 ( 1986. ). [DOI] [PubMed] [Google Scholar]
- 29. ) Tokuda , H. , Ohigashi , H. , Koshimizu , K. and Ito , Y.Inhibitory effects of ursolic and oleanolic acid on skin tumor promotion by 12‐O‐tetradecanoylphorbol‐13‐acetate . Cancer Lett. , 33 , 279 – 285 ( 1986. ). [DOI] [PubMed] [Google Scholar]
- 30. ) Tamaya , T. , Sato , S. and Okada , H.Inhibition by plant herb extracts of steroid bindings in uterus, liver and serum of the rabbit . Acta Obstet. Gynecol. Scand. , 65 , 839 – 842 ( 1986. ). [DOI] [PubMed] [Google Scholar]