Journal of Physiology & Pathology in Korean Medicine (동의생리병리학회지)

The Physiological Society of Korean Medicine and The Society of Pathology in Korean Medicine (대한동의생리학회·한의병리학회)
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Inhibition of Cellular Proliferation by p53 dependent Apoptosis and G2M Cell Cycle Arrest of Saussurea lappa CLARKE in AGS Gastric Cancer Cell Lines

  • Jeong Han Su (Department of Circulatory Internal medicine, College of Oriental medicine Semyung University) ;
  • Kim Dong Jo (Department of Circulatory Internal medicine, College of Oriental medicine Semyung University) ;
  • Heo Geum Jeong (Department of Circulatory Internal medicine, College of Oriental medicine Semyung University) ;
  • Nam Chang Gyu (Department of Circulatory Internal medicine, College of Oriental medicine Semyung University) ;
  • Go Seong Gyu (Department of Circulatory Internal medicine, College of Oriental medicine Semyung University)
  • Published : 2004.08.01
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Abstract

The root of Saussurea lappa includes sesquiterpene lactones such as costunolide and dehydrocostus lactone, and has been shown to be anti-tumorigenic with being used in traditional medicinal therapy in the Eastern Asia. However, the molecular basis of the effects of Saussurea lappa on fate of gastric carcinoma, which incur very frequently in the area, has not been well identified. In this study, the cytostatic effects of Saussurea lappa were examined using gastric AGS cancer cells. Cell viability was dramatically reduced by Saussurea lappa, in a dose-dependent manner. As time passed after its treatment, apoptotic population was increased and clearly showed G2-arrest. Being consistent, its treatment resulted in maintaining of G1 and S-phase cyclins D1, E, and A even until a significant apoptotic population was observed, for example, at 24h after treatment. However, G2/M phase cyclin B1 was reduced even at 12 h after treatment. In addition, its treatment increased expression of p53, p21/sup Wafl / cyclin dependent kinase inhibitor (CKI), and Bax, resulted in cleavages of procaspase 3 and poly ADP-ribose polymerase(PARP), indicating that such G2 arrest- and apoptosis-related molecules are involved. Therefore, these suggest that extracts of Saussurea lappa root may be a safer and effective reagent to deal with gastric cancers either by traditional herbal therapy or combinational therapy with conventional chemotherapy.

Keywords

References

  1. Planta Med. v.61 Recent studies on the zoopharmacognosy, pharmacology and neurotoxicology of sesquiterpene lactones M Robles;M Aregullin;J West;E Rodriguez
  2. Biol. Pharm. Bull. v.24 Costunolide induces apoptosis by ROS-mediated mitochondrial permeability transition and cytochrome C release MG Lee;KT Lee;SG Chi;JH Park
  3. Cancer Lett. v.83 Chemopreventive effect of costunolide, a constituent of oriental medicine, on azoxymethane-induced intestinal carcinogenesis in rats H Mori;T Kawamori;T Tanaka;M Ohnishi;J Yamahara
  4. Cell Mol.Life Sci. v.59 Regulation of cyclin-Cdk activity in mammalian cells AJ Obaya;JM Sedivy
  5. Curr. Opin. Cell Biol. v.9 Cell anchorage and the cytoskeleton as partners in growth factor dependent cell cycle progression RK Assoian;X Zhu
  6. Curr. Opin. Genet. Dev. v.11 Coordinate signaling by integrins and receptor tyrosine kinases in the regulation of G1 phase cell-cycle progression RK Assoian;MA Schwartz
  7. J. Cell Physiol. v.189 Fibronectin, integrins, and growth control EH Danen;KM Yamada
  8. Annu. Rev. Pharmacol. Toxicol. v.42 Signal transduction by cell adhesion receptors and the cytoskeleton: Functions of Integrins, Cadherins, Selectins, and Immunoglobulin-Superfamily Members RL Juliano
  9. Exp. Cell Res. v.275 A discrete cell cycle checkpoint in late G(1) that is cytoskeleton-dependent and MAP kinase (Erk)-independen S Huang;DE Ingber
  10. Mol. Cell Biol. v.18 Effects of p21(Cip1/Waf1) at both the G1/S and the G2/M cell cycle transitions: pRb is a critical determinant in blocking DNA replication and in preventing endoreduplication AB Niculescu, 3rd;X Chen;M Smeets;L Hengst;C Prives;SI Reed
  11. J. Biol. Chem. v.275 p21 inhibits Thr161 phosphorylation of Cdc2 to enforce the G2 DNA damage checkpoint VA Smits;R Klompmaker;T Vallenius;G Rijksen;TP Makela;RH Medema
  12. Science v.282 Requirement for p53 and p21 to sustain G2 arrest after DNA damage. F Bunz;A Dutriaux;C Lengauer;T Waldman;S Zhou;JP Brown;JM Sedivy;KW Kinzler;B Vogelstein
  13. Mol. Biol. Cell v.11 alpha5beta1 integrin protects intestinal epithelial cells from apoptosis through a phosphatidylinositol 3-kinase and protein kinase B- dependent pathway JW Lee;RL Juliano
  14. Jpn. J. Cancer Res. v.93 Costunolide triggers apoptosis in human leukemia U937 cells by depleting intracellular thiols JH Choi;J Ha;JH Park;JY Lee;YS Lee;HJ Park;JW Choi;Y Masuda;K Nakaya;KT Lee
  15. Toxicology Cell cycle checkpoint signaling: cell cycle arrest versus apoptosis JA Pietenpol;ZA Stewart
  16. Proc. Natl. Acad. Sci. U S A v.96 p53 regulates a G2 checkpoint through cyclin B1 SA Innocente;JL Abrahamson;JP Cogswell;JM Lee
  17. Nature v.401 14-3-3Sigma is required to prevent mitotic catastrophe after DNA damage TA Chan;H Hermeking;C Lengauer;KW Kinzler;B Vogelstein
  18. Proc. Natl. Acad. Sci. USA v.96 GADD45 induction of a G2/M cell cycle checkpoint XW Wang;Q Zhan;JD Coursen;MA Khan;HU Kontny;L Yu;MC Hollander;PM O'Connor;AJ Fornace, Jr.;CC Harris
  19. Proc. Natl. Acad. Sci. USA v.92 Multiple Bcl-2 family members demonstrate selective dimerizations with Bax TW Sedlak;ZN Oltvai;E Yang;K Wang;LH Boise;CB Thompson;SJ Korsmeyer
  20. Mol. Hum. Reprod. v.4 The relationship between BcI2, Bax and p53: consequences for cell cycle progression and cell death A Basu;S Haldar
  21. Eur. Respir. J. no.Sup.39 Early detection of lung cancer: role of biomarkers C Brambilla;F Fievet;M Jeanmart;F de Fraipont;S Lantuejoul;V Frappat;G Ferretti;PY Brichon;D Moro-Sibilot
  22. Oncogene v.9 Tumor suppressor p53 is a regulator of bcl-2 and bax gene expression in vitro and in vivo T Miyashita;S Krajewski;M Krajewska;HG Wang;HK Lin;DA Liebermann;B Hoffman;JC Reed
  23. Cancer Res. v.54 Identification of a p53-dependent negative response element in the bcl-2 gene T Miyashita;M Harigai;M Hanada;JC Reed
  24. Cell v.80 Tumor suppressor p53 is a direct transcriptional activator of the human bax gene T Miyashita;JC Reed
  25. Oncogene v.18 The cellular response to p53: the decision between life and death RV Sionov;Y Haupt
  26. Biochemistry (Mosc) v.68 Caspases as regulators of apoptosis and other cell functions AA Philchenkov
  27. J. Formos. Med. Assoc. v.102 Genetic alterations and polymorphisms in gastric cancer MS Wu;CJ Chen;JT Lin