Archives of Pharmacal Research

  • 제29권8호
  • /
  • Pages.651-656
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  • 2006
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  • 0253-6269(pISSN)
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  • 1976-3786(eISSN)
대한약학회 (The Pharmaceutical Society of Korea)
권호 표지

Chemopreventive Effect of Saponins Derived from Roots of Platycodon grandiflorum on 4-(Methylnitrosamino)-1-(3-Pyridyl)-1-Butanone-Induced Lung Tumorigenesis in A/J Mice

  • Lee, Kyung-Jin (Department of Pharmacy, College of Pharmacy, Research Center for Proteineous Materials, Chosun University) ;
  • Shin, Dong-Weon (Department of Pharmacy, College of Pharmacy, Research Center for Proteineous Materials, Chosun University) ;
  • Chung, Young-Chul (Division of Food Science, Chinju International University) ;
  • Jeong, Hye-Gwang (Department of Pharmacy, College of Pharmacy, Research Center for Proteineous Materials, Chosun University)
  • 발행 : 2006.08.01
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초록

This study examined the chemopreventive effect of saponins that were isolated from the roots of Platycodon grandiflorum A. DC (Campanulaceae), Changkil saponins (CKS), against the tobacco-specific carcinogen, 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK), -on lung tumorigenesis in A/J mice. The mice were treated with a single NNK dose (100 mg/kg b.w., i.p.). CKS (0.5, 1, 4 mg/kg body wt.) was administered orally daily for 3 days/week beginning 1 day after the NNK treatment and was maintained throughout the experiment. The administration of CKS suppressed the NNK-induced increase in the level of proliferating cell nuclear antigen, which are a marker of cell proliferation, in the lungs of the mice 4 weeks after the NNK injection. Twenty-five weeks after the NNK treatment, the mice were sacrificed and the number of surface lung tumors was measured. CKS significantly reduced the number of lung tumors induced by NNK in a dose dependent manner. These results suggest that CKS suppresses the development of lung tumors and has a chemopreventive effect against NNK-induced mouse lung tumorigenesis.

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참고문헌

  1. Belinsky, S. A., Devereux, T. R., and Anderson, M. W., Role of DNA methylation in the activation of proto-oncogenes and the induction of pulmonary neoplasia by nitrosamines. Mutat. Res., 233, 101-116 (1990)
  2. Belinsky, S. A., Devereux, T. R., Foley, J. F., Maronpot, R. R., and Anderson, M. W., Role of the alveolar type II cell in the development and progression of pulmonary tumors induced by 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone in the A/J mouse. Cancer Res., 52, 3164-3173 (1992)
  3. Block, G., Patterson, B., and Subar, A., Fruit, vegetables, and cancer prevention: a review of the epidemiological evidence. Nutr. Cancer, 18, 1-29 (1992) https://doi.org/10.1080/01635589209514201
  4. Castonguay, A. and Rioux, N., Inhibition of lung tumorigenesis by sulindac: comparison of two experimental protocols. Carcinogenesis., 18, 491-496 (1997) https://doi.org/10.1093/carcin/18.3.491
  5. Cerutti, P. A., Oxy-radicals and cancer. Lancet, 344, 862-863 (1994) https://doi.org/10.1016/S0140-6736(94)92832-0
  6. Choi, C. Y., Kim, J. Y., Kim, Y. S., Chung, Y. C., Hahm, K. S., and Jeong, H. G., Augmentation of macrophage functions by an aqueous extract isolated from Platycodon grandiflorum. Cancer Lett., 166, 17-25 (2001) https://doi.org/10.1016/S0304-3835(01)00440-2
  7. De Flora, S., Cesarone, C. F., Balansky, R. M., Albini, A., D'Agostini, F., Bennicelli, C., Bagnasco, M., Camoirano, A., Scatolini, L., and Rovida, A., Chemopreventive properties and mechanisms of N-Acetylcysteine. The experimental background. J. Cell. Biochem Suppl., 22 (Suppl.), 33-41 (1995)
  8. Hall, P. A., Levison, D. A., Woods, A. L., Yu, C. C., Kellock, D. B., Watkins, J. A., Barnes, D. M., Gillett, C. E., Camplejohn, R., Dover, R, Waseem, N. H., and Lane, D. P., Proliferating cell nuclear antigen (PCNA) immuno-localization in paraffin sections: an index of cell proliferation with evidence of deregulated expression in some neoplasms. J. Pathol., 162, 285-294 (1990) https://doi.org/10.1002/path.1711620403
  9. Hecht, S. S., Recent studies on mechanisms of bioactivation and detoxification of 4-(methylnitrosamino)-1-(3-pyridyl)-1- butanone (NNK), a tobacco-specific lung carcinogen. Crit. Rev. Toxicol., 26, 163-181 (1996) https://doi.org/10.3109/10408449609017929
  10. Hecht, S. S. and Hoffmann, D., Tobacco-specific nitrosamines, an important group of carcinogens in tobacco and tobacco smoke. Carcinogenesis, 9, 875-884 (1988) https://doi.org/10.1093/carcin/9.6.875
  11. Hecht, S. S., Morse, M. A., Amin, S., Stoner, G. D., Jordan, K. G., Choi, C. I., and Chung, F. L., Rapid single-dose model for lung tumor induction in A/J mice by 4-(methylnitrosamino)-1- (3-pyridyl)-1-butanone and the effect of diet. Carcinogenesis, 10, 1901-1904 (1989) https://doi.org/10.1093/carcin/10.10.1901
  12. Higaki, I., Matsui-Yuasa, I., Terakura, M., Kinoshita, H., and Otani, S., Increase in ornithine decarboxylase activity caused by hepatocyte growth factor in primary cultured adult rat hepatocytes. Hepatology, 17, 99-102 (1993) https://doi.org/10.1002/hep.1840170118
  13. Hoffmann, D., Rivenson, A., and Hecht, S. S., The biological significance of tobacco-specific N-nitrosamines: smoking and adenocarcinoma of the lung. Crit. Rev. Toxicol., 26, 199-211 (1996) https://doi.org/10.3109/10408449609017931
  14. Irani, K., Xia, Y., Zweier, J. L., Sollott, S. J., Der, C. J., Fearon, E. R., Sundaresan, M., Finkel, T., and Goldschmidt-Clermont, P. J., Mitogenic signaling mediated by oxidants in rastransformed fibroblasts. Science, 275, 1649-1652 (1997) https://doi.org/10.1126/science.275.5306.1649
  15. Kim, K. S., Ezaki, O., Ikemoto, S., and Itakura, H., Effects of Platycodon grandiflorum feeding on serum and liver lipid concentrations in rats with diet-induced hyperlipidemia. J. Nutr. Sci, Vitaminol., 41, 485-491 (1995) https://doi.org/10.3177/jnsv.41.485
  16. Kim, Y. P., Lee, E. B., Kim, S. Y., Li, D., Ban, H. S., Lim, S. S., Shin, K. H., and Ohuchi, K., Inhibition of prostaglandin E2 production by platycodin D isolated from the root of Platycodon grandiflorum. Planta Med., 67, 362-364 (2001) https://doi.org/10.1055/s-2001-14317
  17. Lee, E. B., Pharmacological studies on Platycodon grandiflorum A. DC. IV. A comparison of experimental pharmacological effects of crude platycodin with clinical indications of platycodi radix. Yakugaku Zasshi, 93, 1188- 1194 (1973) https://doi.org/10.1248/yakushi1947.93.9_1188
  18. Lee, K. J. and Jeong, H. G., Protective effect of Platycodi radix on carbon tetrachloride-induced hepatotoxicity. Food Chem. Toxicol., 40, 517-525 (2002) https://doi.org/10.1016/S0278-6915(01)00104-1
  19. Lee, K. J., Kim, J. Y., Jung, K. S., Choi, C. Y., Chung, Y. C., Kim, D. H., and Jeong, H. G., Suppressive effects of Platycodon grandiflorum on the progress of carbon tetrachloride-induced hepatic fibrosis. Arch. Pharm. Res., 27, 1238-1244 (2004a) https://doi.org/10.1007/BF02975888
  20. Lee, K. J., Choi, C. Y., Chung, Y. C., Kim, Y. S., Ryu, S. Y., Roh, S. H., and Jeong, H. G., Protective effect of saponins derived from roots of Platycodon grandiflorum on tert-butyl hydroperoxide- induced oxidative hepatotoxicity. Toxicol. Lett., 147, 271-282 (2004b) https://doi.org/10.1016/j.toxlet.2003.12.002
  21. Lee, K. J., You, H. J., Park, S. J., Kim, Y. S., Chung, Y. C., Jeong, T. C., and Jeong, H. G., Hepatoprotective effects of Platycodon grandiflorum on acetaminophen-induced liver damage in mice. Cancer Lett., 174, 73-81 (2001) https://doi.org/10.1016/S0304-3835(01)00678-4
  22. Lubet, R. A, Zhang, Z., Wiseman, R. W., and You, M., Use of p53 transgenic mice in the development of cancer models for multiple purposes. Exp. Lung Res., 26. 581-593 (2000) https://doi.org/10.1080/01902140150216684
  23. Nguyen, V. N., Mirejovsky, P., Mirejovsky, T., Melinova, L., and Mandys, V., Expression of cyclin Dl, Ki-67 and PCNA in nonsmall cell lung cancer: prognostic significance and comparison with p53 and bcl-2. Acta Histochem., 102, 323- 338 (2000) https://doi.org/10.1078/S0065-1281(04)70039-2
  24. Okudela, K., Hayashi, H., Ito, T., Yazawa, T., Suzuki, T., Nakane, Y., Sato, H., Ishi, H., KeQin, X., Masuda, A., Takahashi, T., and Kitamura, H., K-ras gene mutation enhances motility of immortalized airway cells and lung adenocarcinoma cells via Akt activation: possible contribution to non-invasive expansion of lung adenocarcinoma. Am. J. Pathol., 164, 91-100 (2004) https://doi.org/10.1016/S0002-9440(10)63100-8
  25. Park, D. I., Lee, J. H., Moon, S. K., Kim, C. H. , Lee, Y. T., Cheong. J., Choi, B. T., and Choi, Y. H., Induction of apoptosis and inhibition of telomerase activity by aqueous extract from Platycodon grandiflorum in human lung carcinoma cells. Pharmacol Res., 51, 437-443 (2005) https://doi.org/10.1016/j.phrs.2004.11.003
  26. Rioux, N. and Castonguay, A., Prevention of NNK-induced lung tumorigenesis in A/J mice by acetylsalicylic acid and NS-398. Cancer Res., 58, 5354-5360 (1998)
  27. Ronai, Z. A., Gradia, S., Peterson, L. A., Hecht, S. S., G to A transitions and G to T transversions in codon 12 of the Ki-ras oncogene isolated from mouse lung tumors induced by 4- (methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) and related DNA methylating and pyridyloxobutylating agents. Carcinogenesis, 14, 2419-2422 (1993) https://doi.org/10.1093/carcin/14.11.2419
  28. Said, T. K. and Medina, D., Cell cyclins and cyclin-dependent kinase activities in mouse mammary tumor development. Carcinogenesis, 16, 823-830 (1995) https://doi.org/10.1093/carcin/16.4.823
  29. Shivji, K. K., Kenny, M. K., and Wood, R. D., Proliferating cell nuclear antigen (PCNA) is required for DNA excision repair. Cell, 69, 367-374 (1992) https://doi.org/10.1016/0092-8674(92)90416-A
  30. Tada, A., Kaneiwa, Y., Shoji, J., and Shibata, S., Studies on the saponins of the root of Platycodon grandiflorum. A. DE CANDOLLE. I: Isolation and the structure of Platycodin-D. Chem. Pharm. Bull., 23, 2965-2972 (1975) https://doi.org/10.1248/cpb.23.2965
  31. van Zandwijk, N., N-acetylcysteine (NAC) and glutathione (GSH): antioxidant and chemopreventive properties, with special reference to lung cancer. J. Cell. Biochem., 22 (Suppl.), 24-32 (1995)
  32. Voorrips, L. E., Goldbohm, R. A., Brants, H. A., van Poppel, G. A., Sturmans, F., Hermus, R. J., and van den Brandt, P. A., A prospective cohort study on antioxidant and folate intake and male lung cancer risk. Cancer Epidemiol. Biomarkers Prev., 9, 357-365 (2000)
  33. Wattenberg, L. W., Chemoprevention of cancer. Cancer Res., 45, 1-8 (1985) https://doi.org/10.1016/S0065-230X(08)60265-1
  34. Xu, Y., Ho, C. T., Amin, S. G., Han, C., and Chung, F. L., Inhibition of tobacco-specific nitrosamine-induced lung tumorigenesis in A/J mice by green tea and its major polyphenol as antioxidants. Cancer Res., 52, 3875-3879 (1992)
  35. Ziegel, R., Shallop, A., Jones, R., and Tretyakova, N., K-ras, gene sequence effects on the formation of 4-(methylnitrosamino)- 1(3-pyridyl)-1-butanone (NNK)-DNA adducts. Chem. Res. Toxicol., 16, 541-550 (2003) https://doi.org/10.1021/tx025619o