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Japanese Journal of Cancer Research : Gann logoLink to Japanese Journal of Cancer Research : Gann
. 1997 Feb;88(2):111–119. doi: 10.1111/j.1349-7006.1997.tb00355.x

Inhibitory Effects of Dietary Protocatechuic Acid and Costunolide on 7,12‐Dimethylbenz[a]anthracene‐induced Hamster Cheek Pouch Carcinogenesis

Masami Ohnishi 1,, Naoki Yoshimi 2, Toshihiko Kawamori 2, Natsuko Ino 2, Yoshinobu Hirose 2, Takuji Tanaka 2, Johji Yamahara 3, Hideo Miyata 1, Hideki Mori 2
PMCID: PMC5921359  PMID: 9119738

Abstract

The modifying effects of dietary exposure to two natural products, protocatechuic acid (PCA) and Costunolide during the development of neoplasms in oral carcinogenesis initiated with 7,12‐dimethyl‐benz[a]anthracene (DMBA) were investigated in male Syrian golden hamsters. All hamsters except those in the test chemical alone and control groups received DMBA (0.5%) in mineral oil to the right buccal pouch 3 times per week for 4 or 6 weeks. At 13 weeks of age, the groups exposed to DMBA were fed diet containing PCA or Costunolide at a dose of 0.2 g/kg diet (200 ppm) for 17 weeks. The other groups consisted of hamsters given mineral oil alone for 6 weeks, or given 200 ppm PCA or Costunolide alone, or untreated. All animals were necropsied at the termination of the experiment (week 24). PCA or costunolide significantly decreased the tumor burden (P<0.001‐P<0.05) and the extent of dysplastic areas (%) (P<0.001‐P<0.05). PCA significantly decreased the mean number of AgNORs/nucleus (P<0.05). The BrdUrd‐labeling index was reduced by dietary administration of test compounds, though not significantly. These results suggest that PCA and costunolide inhibited hamster buccal pouch carcinogenesis and such inhibition may be related to suppression of cell proliferation in the buccal mucosa. It was also found that telomerase activity expressed in neoplastic and preneoplastic lesions of hamster buccal pouch epithelium after DMBA treatment correlated with the histopathological degree of malignancy.

Keywords: 7,12‐Dimethylbenz [a] anthracene; Hamster cheek pouch carcinogenesis; Protocatechuic acid; Costunolide; Telomerase activity

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REFERENCES

  • 1. ) Slaughter , D. P. , Southwick , H. W. and Smejkal , W.Field cancerization in oral stratified squamous epithelium: clinical implications of multicentric origin . Cancer , 6 , 963 – 968 ( 1953. ). [DOI] [PubMed] [Google Scholar]
  • 2. ) Hong , W. K. , Lippman , S. M. and Wolf , G. T.Recent advances in head and neck cancer – larynx preservation and cancer chemoprevention: the seventeenth Annual Richard and Hinda Rosenthal Foundation Award Lecture . Cancer Res. , 53 , 5113 – 5120 ( 1993. ). [PubMed] [Google Scholar]
  • 3. ) Tanaka , T. , Kojima , T. , Okumura , A. , Yoshimi , N. and Mori , H.Alterations of the nucleolar organizer regions during 4‐nitroquinoline 1‐oxide‐induced tongue carcinogenesis in rats . Carcinogenesis , 12 , 329 – 333 ( 1991. ). [DOI] [PubMed] [Google Scholar]
  • 4. ) Kotwall , C. , Razack , M. S. , Sake , K. and Rao , U.Multiple primary cancers in squamous cell cancers of the head and neck . J. Surg. Oncol , 40 , 97 – 99 ( 1989. ). [DOI] [PubMed] [Google Scholar]
  • 5. ) Lippman , S. M. and Hong , W. K.Second malignant tumors in head and neck squamous cell carcinoma: the overshadowing threat for patients with early‐stage disease . Int. J. Radiat. Oncol Biol Phys. , 17 , 691 – 694 ( 1989. ). [DOI] [PubMed] [Google Scholar]
  • 6. ) Wallenberg , L. W.In “ Chemoprevention of Cancer by Naturally Occurring and Synthetic Compounds ,” ed. Wallenberg L. W. , Lipkin M. , Boone C. W. , and Kelloff G. J. , pp. 19 – 39 ( 1992. ). CRC Press; , Boca Raton , FL . [Google Scholar]
  • 7. ) Tanaka , T.Chemoprevention of oral carcinogenesis . Oral Oncol Eur. J. Cancer , 31B , 3 – 15 ( 1995. ). [DOI] [PubMed] [Google Scholar]
  • 8. ) Mori , H. , Tanaka , T. , Sugie , S. and Yoshimi , N.Chemopreventive effects of plant derived phenolic, organosulfur and other compounds on carcinogenesis in digestive organs . Environ. Mutagen Res. Commun. , 17 , 127 – 133 ( 1995. ). [Google Scholar]
  • 9. ) Ueno , A.The studies on the constituenls and the utilization in Citrus species . Foods Food Ingredients J. 157 , 46 – 53 ( 1993. ), in Japanese . [Google Scholar]
  • 10. ) Tanaka , T. , Kojima , T. , Kawamori , T. , Yoshimi , N. and Mori , H.Chemoprevention of diethylnilrosamine‐induced hepatocarcinogenesis by a simple phenolic acid, protocate‐chuic acid, in rals . Cancer Res. , 53 , 2775 – 2779 ( 1993. ). [PubMed] [Google Scholar]
  • 11. ) Tanaka , T. , Kojima , T. , Suzui , M. and Mori , H.Chemoprevention of colon carcinogenesis by the natural product of a simple phenolic compound, protocatechuic acid: suppressing effects on tumor development and biomarkers expression of colon tumorigenesis . Cancer Res. , 53 , 3908 – 3913 ( 1993. ). [PubMed] [Google Scholar]
  • 12. ) Tanaka , T. , Kawamori , T. , Ohnishi , M. , Okamoto , K. , Mori , H. and Kara , A.Chemoprevention of 4‐nitroquino‐line 1‐oxide‐induced oral carcinogenesis by dietary protocatechuic acid during initiation and postinitiation phases . Cancer Res. , 54 , 2359 – 2365 ( 1994. ). [PubMed] [Google Scholar]
  • 13. ) Mori , H. , Sugie , S. , Tanaka , T. , Makita , H. and Yoshimi , N.Suppressive effects of natural antioxidants on carcinogenesis in digestive organs . Environ. Mutagen Res. Commun. , 18 , 73 – 77 ( 1996. ). [Google Scholar]
  • 14. ) Yamahara , J. , Kobayasi , K. , Miki , K. , Kozuka , M. , Sawada , T. and Fujimura , H.Cholagogic and antiulcer effect of Saussureae Radix and its active components . Chem. Pharm. Bull , 33 , 1285 – 1288 ( 1985. ). [DOI] [PubMed] [Google Scholar]
  • 15. ) Yoshikawa , M. , Hatakeyama , S. , Inoue , Y. and Yamahara , J.Saussureamines A, B, C, D and E, new anti‐ulcer principles from Chinese Saussureae Radix . Chem. Pharm. Bull , 41 , 214 – 216 ( 1993. ). [DOI] [PubMed] [Google Scholar]
  • 16. ) Mori , H. , Kawamori , T. , Tanaka , T. , Ohnishi , M. and Yamahara , J.Chemopreventive effect of costunolide, a constituent of oriental medicine, on azoxymethaneinduced intestinal carcinogenesis in rats . Cancer Lett , 83 , 171 – 175 ( 1994. ). [DOI] [PubMed] [Google Scholar]
  • 17. ) Gimenez‐Conti , I. B. and Slaga , T. J.The hamster cheek pouch carcinogenesis model . J. Cell. Biochem. , 17F ( Suppl. ), 83 – 90 ( 1993. ). [DOI] [PubMed] [Google Scholar]
  • 18. ) Suda , D. , Schwartz , J. and Shklar , G.Inhibition of experimental oral carcinogenesis by topical beta carotene . Carcinogenesis , 7 , 711 – 715 ( 1986. ). [DOI] [PubMed] [Google Scholar]
  • 19. ) Shklar , G. , Schwartz , J. , Trickier , D. P. and Niukian , K.Regression by vitamin E of experimental oral cancer . J. Natl. Cancer Inst. , 78 , 987 – 992 ( 1987. ). [PubMed] [Google Scholar]
  • 20. ) Shklar , G. , Schwartz , J. , Grau , D. , Trickier , D. P. and Wallance , K. D.Inhibition of hamster buccal pouch carcinogenesis by 13‐cis‐retinoic acid . Oral Surg. , 50 , 45 – 52 ( 1980. ). [DOI] [PubMed] [Google Scholar]
  • 21. ) Burge‐Bottenbley , A. and Shklar , G.Retardation of experimental oral cancer development by retinyl acetate . Nutr. Cancer , 5 , 121 – 129 ( 1983. ). [DOI] [PubMed] [Google Scholar]
  • 22. ) Blackburn , E. H.Structure and function of telomeres . Nature , 350 , 569 – 573 ( 1991. ). [DOI] [PubMed] [Google Scholar]
  • 23. ) Blackburn , E. H.Telomeres . Trends Biochem. Sci. , 16 , 378 – 381 ( 1991. ). [DOI] [PubMed] [Google Scholar]
  • 24. ) Allsopp , R. C. , Vaziri , H. , Patterson , C. , Goldstein , S. , Younglai , E. V. , Futcher , A. B. , Greider , C. W. and Harley , C. B.Telomere length predicts replicative capacity of human fibroblasts . Proc. Natl. Acad. Sci. USA , 89 , 10114 – 10118 ( 1992. ). [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 25. ) Watson , J. D.Origin of concatemeric T7 DNA . Nature , 350 , 569 – 573 ( 1972. ). [DOI] [PubMed] [Google Scholar]
  • 26. ) Greider , C. W.Telomerase is processive . Mol. Cell. Biol , 11 , 4572 – 4580 ( 1991. ). [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 27. ) Feng , J. , Funk , W. D. and Wang , S. S.The RNA component of human telomerase . Science , 269 , 1236 – 1241 ( 1995. ). [DOI] [PubMed] [Google Scholar]
  • 28. ) Harley , C. B. and Villeponteau , B.Telomeres and telomerase in aging and cancer . Curr. Opin. Genet. Dev. , 5 , 249 – 255 ( 1995. ). [DOI] [PubMed] [Google Scholar]
  • 29. ) Bánóczy , J. and Csiba , A.Occurrence of epithelial dysplasia in oral leukoplakia . Oral Surg. , 42 , 766 – 774 ( 1976. ). [DOI] [PubMed] [Google Scholar]
  • 30. ) WHO Collaborating Center for oral precancerous lesions: definition of leukoplakia and related lesions: an aid to studies on oral precancer . Oral Surg. , 46 , 518 – 539 ( 1978. ). [PubMed] [Google Scholar]
  • 31. ) Tanaka , T.Cancer Chemoprevention . Cancer J. , 5 , 11 – 16 ( 1992. ). [Google Scholar]
  • 32. ) Kim , N. W. , Piatyszek , M. A. , Prowse , K. R. , Harley , C. B. , West , M. D. , Ho , P. L. C. , Coviello , G. M , Wright , W. E. , Weinrich , S. L , and Shay , J. W.Specific association of human telomerase activity with immortal cells and cancer . Science 266 , 2011 – 2015 ( 1994. ). [DOI] [PubMed] [Google Scholar]
  • 33. ) Yoshimi , N. , Ino , N. , Suzui , M. , Hara , A. , Nakatani , K. , Sato , S. and Mori , H.Telomerase activity of normal tissues and neoplasms in rat colon carcinogenesis induced by methylazoxymethanol acetate and its difference from that of human colonic tissues . Mol. Carcinog. , 16 , 1 – 5 ( 1996. ). [DOI] [PubMed] [Google Scholar]
  • 34. ) Wattenberg , L. W.Chemoprevention of cancer . Cancer Res. , 45 , 1 – 8 ( 1985. ). [PubMed] [Google Scholar]
  • 35. ) Kawamori , T. , Tanaka , T. , Hara , A. , Yamahara , J. and Mori , H.Modifying effects of naturally occurring products on the development of colonic aberrant crypt foci induced by azoxymethane in F344 rats . Cancer Res. , 55 , 1277 – 1282 ( 1995. ). [PubMed] [Google Scholar]
  • 36. ) Cohen , S. M. , and Ellwein , L. B.Cell proliferation and carcinogenesis . Science , 249 , 1007 – 1011 ( 1990. ). [DOI] [PubMed] [Google Scholar]
  • 37. ) Preston‐Martin , S. , Pike , M. C. , Ross , R. K. , Jones , P. A. and Henderson , B. E.Increased cell division as a cause of human cancer . Cancer Res. , 50 , 7415 – 7421 ( 1990. ). [PubMed] [Google Scholar]
  • 38. ) Tanaka , T. , Yoshimi , N‐ , Sugie , S. and Mori , H.In “ Protective Effects against Liver, Colon, and Tongue Carcinogenesis by Plant Phenols ,” ed. Huang M.‐T. , Ho C.‐T. and Lee C.Y. , pp. 326 – 337 ( 1992. ). American Chemical Society; , Washington, DC . [Google Scholar]
  • 39. ) Tanaka , T. , Kojima , T. , Kawamori , T. , Wang , A. , Suzui , M. , Okamoto , K. and Mori , H.Inhibition of 4‐nitroquino‐line 1‐oxide‐induced rat tongue carcinogenesis by the naturally occurring plant phenolics caffeic, ellagic, chlorogenic and ferulic acids . Carcinogenesis , 14 , 1321 – 1325 ( 1993. ). [DOI] [PubMed] [Google Scholar]
  • 40. ) Tanaka , T. , Kojima , T. , Kara , A. , Sawada , H. and Mori , H.Chemoprevention of oral carcinogenesis by DL‐a‐difluoromethylornithine, an ornithine decarboxylase inhibitor: dose‐dependent reduction in 4‐nitroquinoline 1‐oxideinduced tongue neoplasms in rats . Cancer Res. , 53 , 772 – 776 ( 1993. ). [PubMed] [Google Scholar]
  • 41. ) Kipling , D.Telomerase: immortality enzyme or oncogene? [news] . Nat. Genet. , 9 , 104 – 106 ( 1995. ). [DOI] [PubMed] [Google Scholar]
  • 42. ) Chadeneau , C. , Hay , K. , Hirte , H. W. , Gallinger , S. and Bacchetti , S.Telomerase activity associated with acquisition of malignancy in human colorectal cancer . Cancer Res. , 55 , 2533 – 2536 ( 1995. ). [PubMed] [Google Scholar]
  • 43. ) Hiyama , E. , Yokoyama , T. , Tatsumoto , M. , Hiyama , K. , Imamura , Y. , Murakami , Y. , Kodama , T. , Piatyszek , M. A. and Shay , J. W.Telomerase activity in gastric cancer . Cancer Res. , 55 , 3258 – 3262 ( 1995. ). [PubMed] [Google Scholar]
  • 44. ) Tahara , H. , Nakanishi , T. , Kitamoto , T. , Nakashio , R. , Shay , J. W. , Tahara , E. , Kajiyama , G. and Ide , T.Telomerase activity in human liver tissues: comparison between chronic liver disease and hepatocellular carcinomas . Cancer Res. , 55 , 2734 – 2736 ( 1995. ). [PubMed] [Google Scholar]
  • 45. ) Mutirangura , A. , Supiyaphun , P. , Trirekapan , S. , Sriuranpong , V. , Sakuntabhai , A. , Yenrudi , S. and Voravud , N.Telomerase activity in oral leukoplakia and head and neck squamous cell carcinoma . Cancer Res. , 56 , 3530 – 3533 ( 1996. ). [PubMed] [Google Scholar]
  • 46. ) Bednarek , A. , Budunova , L , Slaga , T. J. and Aldaz , C. M.Increase telomerase activity in mouth skin premalignant progression . Cancer Res. , 55 , 4566 – 4569 ( 1995. ). [PubMed] [Google Scholar]

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