Skip to main content
Japanese Journal of Cancer Research : Gann logoLink to Japanese Journal of Cancer Research : Gann
. 1992 Dec;83(12):1273–1278. doi: 10.1111/j.1349-7006.1992.tb02758.x

Modifying Effects of Fungal and Herb Metabolites on Azoxymethane‐induced Intestinal Carcinogenesis in Rats

Naoki Yoshimi 1,, Aijin Wang 1, Yukio Morishita 1, Takuji Tanaka 1, Shigeyuki Sugie 1, Kiyoshi Kawai 2, Joji Yamahara 3, Hideki Mori 1
PMCID: PMC5918742  PMID: 1483942

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]

Articles from Japanese Journal of Cancer Research : Gann are provided here courtesy of Wiley

RESOURCES