Effect of Prunella vulgaris L. on Chemopreventive Enzymes of Colorectal Cancer

꿀풀하고초가 직장암 예방효소 활성에 미치는 영향

  • Shon, Yun-Hee (Intractable Disease Research Center, Dongguk University) ;
  • Seo, Jae-Beom (Department of Pharmacology, College of Medicine, Dongguk University) ;
  • Nam, Kyung-Soo (Department of Pharmacology, College of Medicine, Dongguk University)
  • 손윤희 (동국대학교 난치병한양방치료연구센터) ;
  • 서재범 (동국대학교 의과대학 약리학교실) ;
  • 남경수 (동국대학교 의과대학 약리학교실)
  • Published : 2008.02.25

Abstract

Water extract from Prunella vulgaris L. (PVW) was tested for colon cancer chemopreventive activity by measuring the activities of cytochrome P450 1A1, phase Ⅱ detoxification enzyme [quinone reductase (QR) and glutathione S-transferase (GST)] and ornithine decarboxylase (ODC) and glutathione (GSH) levels in cultured human colorectal adenocarcinoma HT-29 cells. PVW significantly inhibited 7,12-dimethylbenz[a]anthracene (DMBA)-induced cytochrome P450 1A1 activity at 10 and 50 ${\mu}g/ml$. PVW induced QR activity in a dose-dependent manner over a concentration range of $1{\sim}50\;{\mu}g/ml$. GST activity was also induced with the treatment of PVW in HT-29 cells. In addition GSH levels were increased with PVW. PVW inhibited ODC activity, a key enzyme of polyamine biosynthesis, which is enhanced in tumor promotion. These results suggest that Prunella vulgaris L. has colon cancer chemopreventive activity by inhibiting cytochrome P450 1A1 and ODC activities and by increasing phase Ⅱ enzyme activity and GSH levels.

Keywords

References

  1. Parkin, D.M., Pisani, P., Ferlay, J. Estimates of the worldwide incidence of eighteen major cancers in 1985. Int. J. Cancer 54: 594-606, 1993 https://doi.org/10.1002/ijc.2910540413
  2. Jollow, D.J., Smith, C. In Jollow, K.J., Kocsis, J.J., Snyder, R., Vainio, H. (eds.), Biologically Reactive Intermediates. Plenum Press. New York, USA, pp 42-59, 1977
  3. Prochaska, H.J., Talalay, P. Regulatory mechanisms of monofunctional and bifuncitonal anticarcinogenic enzyme inducers in murine liver. Cancer Res. 48: 4776-4782, 1988
  4. Mitchell, J.R., Hinson, J.A., Nelson, S.D. Glutathione and drug induced tissue lesions: metabolism and function, In Arias, I. M. and W.B. Jakoby (eds.), Glutathiones, Raven Press. New York, USA, pp 357-367, 1976
  5. Li, L., Carol, T., Susan, K.G. Inhibition of ornithine decarboxylase (ODC) decreases tumor vascularization and reverse spontaneous tumors in ODC/Ras transgenic mice. Cancer Res. 60: 5696-5730, 2000
  6. Tanako, T., Kojima, T., Suzuki, M., 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. Cancer Res. 53: 3908-3913, 1993
  7. 吳 普. 神農本草經. 台北, 臺灣中華書局, pp 19-20, 1990
  8. 金昌玟. 本草學. 서울, 韓國生藥學敎授協議會, pp 166-168, 1994
  9. 김주선, 강삼식, 이경순, 장승엽, 원도희. 하고초 (夏枯草, Prunellae Herba)로부터 Ursolic acid의 함량분석. 생약학회지 31: 416-420, 2001
  10. Pohl, R.J., Fouts, J.R. A rapid method for assaying the metabolism of 7-ethoxyresorufin by microsomal subcellular fractions. Anal. Biochem. 107: 150-155, 1980 https://doi.org/10.1016/0003-2697(80)90505-9
  11. Rodrigues, A.D., Prough, R.A. Induction of cytochromes P450 1A1 and P450 1A2 and measurement of catalytic activities. Methods Enzymol. 206: 423-431, 1991 https://doi.org/10.1016/0076-6879(91)06111-F
  12. Prochaska, H.J., Santamaria, A.B. Direct measurement of NAD(P)H:Quinone reductase from cells cultured in microtiter wells: A screening assay for anticarcinogenic enzyme inducers. Anal. Biochem. 169: 328-336, 1988 https://doi.org/10.1016/0003-2697(88)90292-8
  13. 윤성묵, 조경희, 손윤희, 남경수, 임종국. 생약 약침액에 의한 phase II 효소 활성 유도. 대한경락경혈학회지 18: 1-9, 2001
  14. Sindhu, R.K., Mitsuhashi, M., Kikkawa, Y. Inhibition of cytochrome P450 1A1 by antisense phosphorothioate oligonucleotide in Hepalclc7 cells. Biochem. Biophys. Res. Commun. 229: 673-680, 1996 https://doi.org/10.1006/bbrc.1996.1862
  15. Inouye, K., Mae, T., Kondo, S., Ohkawa, H. Inhibitory effects of vitamin A and vitamin K on rat cytochrome P4501A1-dependent monooxygenase activity. Biochem Biophys Res Commun. 262: 565-569, 1999 https://doi.org/10.1006/bbrc.1999.1240
  16. Wattenberg, L.W., Bueding, E. Inhibitory effect of 5-(2-pyrazinyl)-4- methyl-1,2-dithiol-3-thione (oltipraz) on carcinogenesis induced by benzo(a)- pyrene, diethlnitrosamine, and uracil mustard. Carcinognesis 7: 1379-1381, 1986 https://doi.org/10.1093/carcin/7.8.1379
  17. Talalay, P., Fahey, J.W., Holtzclaw, W.D., Prestera, T., Zhang, Y. Chemoprotection against cancer by phase II enzyme induction. Toxicol. Lett. (Amst.) 82: 173-179, 1995
  18. Marton, L.J., Pegg, A.E. Polyamines as targets for therapeutic intervention. Annu. Rev. Pharmacol. Toxicol. 35: 55-91, 1995 https://doi.org/10.1146/annurev.pa.35.040195.000415