Journal of Society of Preventive Korean Medicine (대한예방한의학회지)

Society of Preventive Korean Medicine (대한예방한의학회)
권호 표지

The antitumor activities of Acanthopanax senticosus Harms(ASH) in human gastric cancer AGS cell lines

가시오가피 에탄올추출물의 AGS위암세포주에서 세포주기억제효과

  • 이선동 (상지대학교 한의과대학 예방의학교실) ;
  • 고성규 (경희대학교 한의과대학 예방의학교실) ;
  • 신헌태 (동신대학교 한의과대학 예방의학교실) ;
  • 신용철 (경희대학교 한의과대학 예방의학교실)
  • Received : 2011.09.15
  • Accepted : 2011.12.07
  • Published : 2011.12.31
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Abstract

Objectives : The research was conducted to confirm the effect of Acanthopanax senticosus harms(ASH) on the anti-tumor activities in AGS human gastric cancer cells. Methods : To examine the potential anti-tumor effect of ASH, we performed many experiments. After processing AGS cancer cells with varying concentrations 80% ethanol ASH extract, analyses by MTT, flow cytometer(FACS) and western blot were used. Results : AGS cancer cells showed decreased cell proliferation and increased contents of S phase when treated with ASH. Moreover, the Western blot experiment showed that ASH affected S phase cell cycle-related molecules(Cyclin A, p21 and p16) in AGS cells. ASH also inhibited EGFR-STAT3 pathway in AGS human gastric cancer cells. Conclusion : Based on these results, we observed that ASH arrested the cell cycle at S phase and inhibited the phosphorylation of EGFR and STAT3 proteins which reduce the cell cycle and the manifestation of the genes that are related to inhibiting cell growth in AGS cells. It can be concluded that ASH can be used in developing medicine for gastric cancer.

Keywords

References

  1. Hu, P.J., Yu, J., Zeng, Z.R., Leung, W.K., Lin, H.L., Tang, B.D., Bai, A.H. and Sung, J.J. Chemoprevention of gastric cancer by celecoxib in rats. Gut 53(2) : 195-200, 2004. https://doi.org/10.1136/gut.2003.021477
  2. Kelley, J.R. and Duggan, J.M. Gastric cancer epidemiology and risk factors. J. Clin.Epidemiol. 56(1) : 1-9, 2003. https://doi.org/10.1016/S0895-4356(02)00534-6
  3. Parkin, D.M., Whelan, S.L., Ferlay, J., et al. Cancer incidence in five continents. Lyon : International Agency for Research on Cancer 7 : 822-831, 1997.
  4. Ministry for Health, Welfare and Family Affairs. Annual report of Cancer incidence (2007), cancer prevalence(2007), and survival(1993-2007) in Korea. 2009.
  5. Yonsei Cancer Center. Report of Yonsei Cancer Center. 2008.
  6. Howson, C.P., Hiyama, T. and Wynder, E.L. The decline in gastric cancer : epidemiology of an unplanned triumph. Epidemiol. Rev. 8 : 1-27, 1986.
  7. Nasmyth. Viewpoint : putting the cell cycle in order. Science 274(5293) : 1643-1645, 1996. https://doi.org/10.1126/science.274.5293.1643
  8. Lee, J.H., Kim, Y.C. and Woo, H.J. Study on the anti-cancer effect of Acanthopanax Sessiliflorus J. Korean Oriental Med. 20(3) : 464-475 1999.
  9. Malumbres and Barbacid. Cell cycle, CDKs and cancer : a changing paradigm. Nat. Rev.Cancer. 9(3) : 153-166, 2009.
  10. Deyama, T., Nishibe, S. and Nakazawa, Y. Constituents and pharmacological effects of Eucommia and Siberian ginseng. Acta Pharmacol.Sin. 22(12) : 1057-1070, 2001.
  11. Soya, H., Deocaris, C.C., Yamaguchi, K., Ohiwa, N., Saito, T., Nishijima, T., Kato, M., Tateoka, M., Matsui, T., Okamoto, M. and Fujikawa, T. Extract from Acanthopanax senticosus harms(Siberian ginseng) activates NTS and SON/PVN in the rat brain. Biosci.Biotechnol.Biochem. 72(9) : 2476-2480, 2008. https://doi.org/10.1271/bbb.80209
  12. The Pharmacopoeia Commission of PRC, "Chinese Pharmacopoeia", Chemical Industry Press, Beijing, China, p 143, 2005.
  13. Zhao, M., Wang, Y., and Kang, L. Chin. J. Chin. Materia Medica 26 : 2001.
  14. Zhou, Y.L., Dong, S.L. and Nie, S.Q. Flora of Woods in Heilongjiang Province, Harbin, China, Heilongjiang Scientific and Technical Press, 1986.
  15. Zgorka, G. and Kawka, S., J. Pharm. Biomed. Anal. 24 : 1605, 2001.
  16. Chen, M.L., Song, F.R., Guo, M.Q., Liu, Z.Q. and Liu, S.Y. Rapid Commun. Mass Spectrom, 2002.
  17. Zhang, S.M., Wang, H.W. and Liu, Y.Q. J. Shenyang Pharm. Univ., 1996.
  18. Davydov, M. and Krikorian, A.D. Eleutherococcus senticosus(Rupr. & Maxim.) Maxim. (Araliaceae) as an adaptogen : a closer look. J.Ethnopharmacol. 72(3) : 345-393, 2000. https://doi.org/10.1016/S0378-8741(00)00181-1
  19. Brekhman I. I., Invest. Sibir. Otdel. Acad. Nauk. U.S.S.R. 9, 113-117, 1969.
  20. Yi, J.M., Hong, S.H., Kim, J.H., Kim, H.K., Song, H.J., Kim, H.M., J. Ethnopharm 79 : 347-352, 2002. https://doi.org/10.1016/S0378-8741(01)00403-2
  21. Lin, C.C. and Huang, P.C. Antioxidant and hepatoprotective effects of Acathopanax senticosus. Phytother.Res. 14(7) : 489-494, 2000. https://doi.org/10.1002/1099-1573(200011)14:7<489::AID-PTR656>3.0.CO;2-G
  22. Jung, H.J., Park, H.J., Kim, R.G., Shin, K.M., Ha, J., Choi, J.W., Kim, H.J., Lee, Y.S. and Lee, K.T. In vivo antiinflammatory and antinociceptive effects of liriodendrin isolated from the stem bark of Acanthopanax senticosus. Planta Med. 69(7) : 610-616, 2003. https://doi.org/10.1055/s-2003-41127
  23. Hibasami, H., Fujikawa, T., Takeda, H., Nishibe, S., Satoh, T., Fujisawa, T. and Nakashima, K. Induction of apoptosis by Acanthopanax senticosus HARMS and its component, sesamin in human stomach cancer KATO III cells. Oncol.Rep. 7(6) : 1213-1216, 2000.
  24. Nishibe, S., Kinoshita, H., Takeda, H. and Okano, G., Phenolic compounds from stem bark of Acanthopanax senticosus and their pharmacological effect in chronic swimming stressed rats. Chemical and Pharmaceutical Bulletin, 1990.
  25. Fujikawa, T., Yamaguchi, A., Morita, I., Takeda, H. and Nishibe, S. Protective effects of Acanthopanax senticosus Harms from Hokkaidoand its components on gastric ulcer in restrained cold water stressed rats. Biol.Pharm.Bull. 19(9) : 1227-1230, 1996. https://doi.org/10.1248/bpb.19.1227
  26. Yi, J.M., Kim, M.S., Seo, S.W., Lee, K.N., Yook, C.S. and Kim, H.M. Acanthopanax senticosus root inhibits mast cell-dependent anaphylaxis. Clin.Chim.Acta 312(1-2) : 163-168, 2001. https://doi.org/10.1016/S0009-8981(01)00613-1
  27. Barranco, S.C., Townsend, C.M.,Jr, Casartelli, C., Macik, B.G., Burger, N.L., Boerwinkle, W.R. and Gourley, W.K. Establishment and characterization of an in vitro model system for human adenocarcinoma of the stomach. Cancer Res. 43(4) : 1703-1709, 1983.
  28. Piontek, M. and Hengels, K.J. Effect of calcium-modifying agents on the growth of human gastric carcinoma cells in vitro. Anticancer Res. 12(5) : 1559-1563, 1992.
  29. Piontek, M. and Hengels, K.J. Effect Evidence for gastrin receptors to mediate stimulatory and for CCK receptors to mediate inhibitory effects on growth of human gastric cancer cells. Gastroenterology. 102(A388) : 1992.
  30. Bull-Henry, K.P., Naab, T.J., Mobley, H.L.T., Resau, J.H. and Smoot, D.T. In vitro gastric epithelial cell invasion by Helicobacter pylori. Gastroenterology 100 (A37) : 1991.
  31. Nilius, M., Bode, G., Buchler, M. and Malfertheiner, P. Adhesion of Helicobacter pylori and Escherichia coli to human and bovine surface mucus cells in vitro. Eur. J.Clin.Invest. 24(7) : 454-459, 1994. https://doi.org/10.1111/j.1365-2362.1994.tb02374.x
  32. Jeong, H.W., Rho, Y.H., Lee, G.S., Kim, C.J. and Jeon, B.G. Experimental effects of Acanthopanacis Cortex extract on the immunity, anti-cancer and obesity in mice. Korean J.Oriental Physiology and Pathology 19(2) : 389-397, 2005.
  33. Cohen, S., Ushiro, H., Stoscheck, C. and Chinkers, M. A native 170,000 epidermal growth factor receptor-kinase complex from shed plasma membrane vesicles. J.Biol.Chem. 257(3) : 1523-1531, 1982.
  34. Shabbir, M. and Stuart, R. Lestaurtinib, a multitargeted tyrosine kinase inhibitor : from bench to bedside. Expert Opin.Investig. Drugs 19(3) : 427-436, 2010. https://doi.org/10.1517/13543781003598862
  35. Zhang, Z., Li, M., Rayburn, E.R., Hill, D.L., Zhang, R. and Wang, H. Oncogenes as novel targets for cancer therapy(part I) : growth factors and protein tyrosine kinases. Am.J.Pharmacogenomics 5(3) : 173-190, 2005.
  36. Craven, R.J., Lightfoot, H. and Cance, W.G. A decade of tyrosine kinases : from gene discovery to therapeutics. Surg. Oncol. 12(1) : 39-49, 2003. https://doi.org/10.1016/S0960-7404(03)00004-5
  37. Darnell, J.E.,Jr, Kerr, I.M. and Stark, G.R. Jak-STAT pathways and transcriptional activation in response to IFNs and other extracellular signaling proteins. Science 264(5164) : 1415-1421, 1994. https://doi.org/10.1126/science.8197455
  38. Fu, X.Y. From PTK-STAT signaling to caspase expression and apoptosis induction. Cell Death Differ. 6(12) : 1201-1208, 1999. https://doi.org/10.1038/sj.cdd.4400613
  39. Park, O.K., Schaefer, T.S. and Nathans, D. In vitro activation of Stat3 by epidermal growth factor receptor kinase. Proc. Natl. Acad. Sci. U.S.A. 93(24) : 13704-13708, 1996. https://doi.org/10.1073/pnas.93.24.13704
  40. Shao, H., Cheng, H.Y., Cook, R.G. and Tweardy, D.J. Identification and characterization of signal transducer and activator of transcription 3 recruitment sites within the epidermal growth factor receptor. Cancer Res. 63(14) : 3923-3930, 2003.
  41. Barre, B., Avril, S. and Coqueret, O. Opposite regulation of myc and p21waf1 transcription by STAT3 proteins. J. Biol. Chem. 278(5) : 2990-2996, 2003. https://doi.org/10.1074/jbc.M210422200
  42. Bowman, T., Broome, M.A., Sinibaldi, D., Wharton, W., Pledger, W.J., Sedivy, J.M., Irby, R., Yeatman, T., Courtneidge, S.A. and Jove, R. Stat3-mediated Myc expression is required for Src transformation and PDGF-induced mitogenesis. Proc. Natl. Acad. Sci. U.S.A. 98(13) : 7319-7324, 2001. https://doi.org/10.1073/pnas.131568898
  43. Karni, R., Jove, R. and Levitzki, A. Inhibition of pp60c-Src reduces Bcl-XL expression and reverses the transformed phenotype of cells overexpressing EGF and HER-2 receptors. Oncogene 18(33) : 4654-4662, 1999. https://doi.org/10.1038/sj.onc.1202835
  44. Shirogane, T., Fukada, T., Muller, J.M., Shima, D.T., Hibi, M. and Hirano, T. Synergistic roles for Pim-1 and c-Myc in STAT3-mediated cell cycle progression and antiapoptosis. Immunity 11(6) : 709-719, 1999. https://doi.org/10.1016/S1074-7613(00)80145-4
  45. Sinibaldi, D., Wharton, W., Turkson, J., Bowman, T., Pledger, W.J. and Jove, R. Induction of p21WAF1/CIP1 and cyclin D1 expression by the Src oncoprotein in mouse fibroblasts : role of activated STAT3 signaling. Oncogene 19(48) : 5419-5427, 2000. https://doi.org/10.1038/sj.onc.1203947
  46. Lo, H.W., Hsu, S.C., Ali-Seyed, M., Gunduz, M., Xia, W., Wei, Y., Bartholomeusz, G., Shih, J.Y. and Hung, M.C. Nuclear interaction of EGFR and STAT3 in the activation of the iNOS/NO pathway. Cancer. Cell. 7(6) : 575-589, 2005. https://doi.org/10.1016/j.ccr.2005.05.007