생명과학회지 (Journal of Life Science)

  • 제13권2호
  • /
  • Pages.154-162
  • /
  • 2003
  • /
  • 1225-9918(pISSN)
  • /
  • 2287-3406(eISSN)
한국생명과학회 (Korean Society of Life Science)
권호 표지
DOI QR코드

DOI QR Code

길경 수용액 추출물에 의한 인체 폐암세포의 apoptosis 유발에 관한 연구

Apoptotic Cell Death of Human Lung Carcinoma A549 Cells by an Aqueous Extract from the Roots of Platycodon grandiflorum

  • 이성열 (동의대학교 한의과대학 내과학교실) ;
  • 이재훈 (동의대학교 한의과대학 생화학교실 및 한의학연구소) ;
  • 김원일 (동의대학교 한의과대학 내과학교실) ;
  • 배송자 (신라대학교 자연과학대학 식품영양학과) ;
  • 박동일 (동의대학교 한의과대학 내과학교실) ;
  • 최영현 (동의대학교 한의과대학 생화학교실 및 한의학연구소)
  • 발행 : 2003.04.01
PDF 다운로드
⟨ 이전 논문 다음 논문 ⟩

초록

전통 한의학에서 많이 사용되는 길경(Platycodi radix)은 도라지(Platycodon grandiflorum A. DC)의 뿌리 껍질을 벗기거나 또는 그대로 말린 것을 말하며, 염증성 호흡기 질환에 많이 사용되어져 오고 있다. 본 연구에서는 길경 수용액 추출물의 항암 활성 기전해석의 일환으로 A549 인체 폐암세포의 성장에 미치는 영향을 조사하였다. 길경 추출물의 처리에 의하여 처리 농도 의존적으로 암세포의 성장이 억제되었으며, 이는 apoptosis의 유발과 관련이 있었다. 즉 염색체 응축에 의한 apoptotic body의 출현과 sub-Gl기에 속하는 세포의 빈도가 길경 추출물 처리에 의하여 농도 의존적으로 증가하였다. Immunoblot 및 RT-PCR분석에서 길경 추출물의 처리에 의하여 Bcl-2의 mRNA 및 단백질의 발현은 감소되었으며, Bax의 발현이 증가됨을 알 수 있었다. 또한 길경 추출물의 처리에 의하여 caspase-3가 활성화되었으며, 이에 따른 PARP 및 $\beta$-catenin의 단백질 발현 감소 현상을 관찰할 수 있었다. 이러한 결과들은 길경 추출물을 이용한 인체 암세포의 성장억제제의 개발 가능성이 있음을 시사하여 준다.

Platycodi Radix, the root of Platycodon grandiflorum, commonly known as Doraji, is used as a traditional oriental medicine. Extracts from the roots of P grandiflorum have been reported to have wide ranging health benefits. In the present study, we investigated the effects of an aqueous extract from the roots of P. grandiflorum (AEPG) on the growth of human lung carcinoma A549 cells. Upon treatment with AEPG, a concentration-dependent inhibition of cell growth was observed and cells developed many of the hallmark features of apoptosis, including condensation of chromatin. Flow cytometry analysis confirmed that AEPG increased populations of apoptotic-sub Gl phase. Immunoblot and quantitative RT-PCR analyses indicated that the expressions of Bcl-2 was down-regulated but Bax was up-regulated in AEPG-treated A549 cells. The expression of active form of caspase-3 by AEPG treatment was markedly increased, and the levels of poly(ADP-ribose) polymerase (PARP) and $\beta$-catenin, its target proteins, were decreased in a concentration dependent manner. Taken together, these findings suggest that P. grandiflorum has strong potential for development as an agent for prevention against human lung cancer.

키워드

참고문헌

  1. Exp. Cell Res. v.256 The Bcl-2 protein family Antonsson,B.;J.C.Martinou https://doi.org/10.1006/excr.2000.4839
  2. Am J. Pathol. v.136 Apoptosis;The role of the endonuclease Arends,M.J.;R.G.Morris;A.H.Wylli
  3. Kor. J. Food Nut. v.9 Studies on immunomodulating function of components separated from Platycodi radix Bae,M.J.;M.H.Park;G.M.Son
  4. Pharmacol. Res. v.29 Cell survival and death programmes Chiarugi,V.L.;Magnelli;A.Turchetti;M.Cinelli;S.Cavari;M.Ruggiero https://doi.org/10.1016/1043-6618(94)80034-0
  5. Cancer Lett. v.166 Augmentation of macrophage functions by an aqueous extract isolated from Platycodon grandiflorum Choi,C.Y.;J.Y.Kim;Y.S.Kim;Y.C.Chung;K.S.Hahm;H.G.Jeong https://doi.org/10.1016/S0304-3835(01)00440-2
  6. Int. Immunopharmacol. v.1 Aqueous extract isolated from Platycodon grandiflorum elicits the release of nitric oxide and tumor necrosis factor-α from murine macrophages Choi,C.Y.;J.Y.Kim;Y.S.Kim;Y.C.Chung;J.K.Seo;H.G.Jeong https://doi.org/10.1016/S1567-5769(01)00047-9
  7. J. Biol. Chem. v.272 Regulation of cyclin D1 by calpain protease Choi,Y.H.;S.J.Lee;P.Nguyen;J.S.Jang;J.Lee;M.L.Wu;E.Takano;M.Maki;P.A.Henkart;J.B.Trepel https://doi.org/10.1074/jbc.272.45.28479
  8. Int. J. Oncol. v.17 Induction of apoptosis by ursolic acid through activation of caspass and down-regulation of c-IAPs in human prostate epithelial cells Choi,Y.H.;J.H.Baek;M.A.Yoo;H.Y.Chung;N.D.Kim;K.W.Kim
  9. Jpn. J. Cancer Res. v.91 p53-independent induction of p21 (WAF1/CIP1), reduction of cyclin B1 and G2/M arrest by the zsoflavone genistein in human prostate carcinoma cells Choi,Y.H.;W.H.Lee;K.Y.Park;L.Zhang https://doi.org/10.1111/j.1349-7006.2000.tb00928.x
  10. Exp. Mol. Med. v.33 Research technics for the cell cycle study Choi,Y.H. https://doi.org/10.1038/emm.2001.3
  11. Int. J. Oncol. v.18 Apoptotic activity of novel bile acid derivatives in human leukemic T cells through the activation of caspasses Choi,Y.H.;E.O.Im;H.S.Suh;Y.E.Jin;W.H.Lee;Y.H.Yoo;K.W.Kim;N.D.Kim
  12. Int. J. Oncol. v.21 Phosphorylation of p53, induction of Bax and activation of caspases during ß-lapachone-mediated apoptosis in human prostate epithelial cells Choi,Y.H.;M.J.Kim;S.Y.Lee;Y.N.Lee;G.Y.Chi;H.S.Eom;N.D.Kim;B.T.Choi
  13. De Candolle. Arg. Chem. Biotech. v.40 Pharmaceutical substances of Platycodon grandiflorum (jacquin) A Chung,J.H.;P.G.Shin;J.C.Ryu;D.S.Jang;S.H.Cho
  14. Acta. Gastroenterol. Belg. v.62 The role of the E-cadherin/catenin complex in gastrointestinal cancer Debruyne,P.;S.Vermeulen;M.Mareel
  15. Curr. Pharm. Biotechnol. v.3 Modulating poly (ADP-ribose) polymerase activity: potential for the prevention and therapy of pathogenic situations involving DNA damage and oxidative stress Decker,P.;S.Muller https://doi.org/10.2174/1389201023378265
  16. Cancer Res. v.54 WAF1/CIP1 is induced in p53-mediated G1 arrest and apoptosis El-Deiry,W.S.;J.W.Harper;P.M.O'Connor;V.E.Velculescu;C.E.Canman;J.Jackman;J.A.Pietenpol;M.Burrell;D.E.Hill;Y.Wang;K.G.Wiman;E.E.Mercer;M.B.Kastan;K.W.Kohn;S.J.Elledge;K.W.Kinzler;B.Vogelstain
  17. Cell Biol. Int. v.17 Multiple pathways to apoptosis Evans,V.G. https://doi.org/10.1006/cbir.1993.1087
  18. Int. J. Biochem. Cell. Biol. v.31 Apoptosis-associated cleavage of β-catenin in human colon cancer and rat hepatoma cells Fukuda,K. https://doi.org/10.1016/S1357-2725(98)00119-8
  19. Int. Immunopharmacol. v.1 Polysaccharide isolated from the radix of Platycodon grandiflorum selectively activates B cells and macrophages but not T cells Han,S.B.;S.H.Park;K.H.Lee;C.W.Lee;S.H.Lee;H.C.Kim;Y.S.Kim;H.S.Lee;H.M.Kim https://doi.org/10.1016/S1567-5769(01)00124-2
  20. Cancer Metastasis. Rev. v.18 Cell adhesion molecules in the development and progression of malignant melanoma Johnson,J.P. https://doi.org/10.1023/A:1006304806799
  21. Cancer Res. v.53 Specific proteolytic cleavage of poly(ADP-ribose) polymerase: an early marker of chemotherapy-induced apoptosis Kaufmann,S.H.;S.Desnoyers;Y.Ottaviano;N.E.Davidson;G.G.Poirier
  22. Shoyakugaku Zasshi J. Pharm. Soc. Jpn. v.40 Immune pharmacological studies on platicodi radix. I. Effect on the phagocytosis in the mouse Kiibo,M.;T.Nagao;H.Matsuda;K.Namba
  23. Planta Med. v.67 Inhibition of prostaglandin E2 production by platycodin D isolated from the root of Platycodon grandiflorum Kim,Y.P.;E.B.Lee;S.Y.Kim;D.Li;H.S.Ban;S.S.Lim;K.H.Shin;K.Ohuchi https://doi.org/10.1055/s-2001-14317
  24. Yakhak Hoeji v.42 Antitumor and immunomodulatroy activities of the Platycodin grandiflorum cultivated for more than 20 years Kim,Y.S.;B.E.Lee;K.J.Kim;Y.T.Lee;K.B.Gho;Y.C.Chung
  25. Nature v.371 Cleavage of poly ADP-ribose polymerase by a proteinase with properties like ICE Lazebnik,Y.A.;S.H.Kaufmann;S.Desnoyers;G.G.Poirier;W.C.Earnshaw https://doi.org/10.1038/371346a0
  26. int. J. Oncol. v.21 Tetrandrine-induced cell cycle arrest and apoptosis in A549 human lung carcinoma cells Lee,J.H.;G.H.Kang;K.C.Kim;K.M.Kim;D.I.Park;B.T.Choi;H.S.Kang;Y.T.Lee;Y.H.Choi
  27. Cancer Lett. v.174 Hepatoprotective effects of Platycodon grandiflorum on acetaminophen-induced liver damage in mice Lee,K.J.;H.J.You;S.J.Park;Y.S.Kim;Y.C.Chung;T.C.Jeong;H.G.Jeong https://doi.org/10.1016/S0304-3835(01)00678-4
  28. J. Pharm. Soc. Korea v.19 Pharmacological activities of crude platycodin Lee,E.B.
  29. Kor. J. Food Sci. Technol. v.30 Effect of Platycodon grandiflorum DC extract on the growth of cancer cell lines Lee,J.Y.;W.I.Hwang;S.T.Lim
  30. Semin. Nephrol. v.18 Necrosis and apoptosis in acute renal failure Lieberthal,W.;J.S.Koh;J.S.Levine
  31. Cell v.80 Tumor suppressor p53 is a direct transcriptional activator of the human bax gene Miyashita,T.;J.C.Reed https://doi.org/10.1016/0092-8674(95)90412-3
  32. Shoyakugaku Zasshi J. Pharm. Soc. Jpn. v.40 Immune pharmacological studies on platicodi radix (Ⅱ);Antitumor activity of inulin from platicodi radix Nagao,T.;H.Matsuda;K.Namba;M.Kubo
  33. Cell v.88 Apoptosis by death factor Nagata,S. https://doi.org/10.1016/S0092-8674(00)81874-7
  34. Biol. Pharm. Bull. v.18 Studies on antiinflammatory effect of Japanese Oriental medicines (kampo medicine) used to treat inflammatory diseases Ozaki,Y. https://doi.org/10.1248/bpb.18.559
  35. Planta Med. v.65 A comparative study on commercial, botanical gardens and wild samples of the roots of Platycodon grandiflorum by HPLC analysis Saeki,T.;K.Koike;T.Nikaido https://doi.org/10.1055/s-1999-14021
  36. Science v.263 Premature p34cdc2 activation required for apoptosis Shi,L.;W.K.Nishioka;J.Th'ng;E.M.Bradbury;D.W.Litchfield;A.H.Greenberg https://doi.org/10.1126/science.8108732
  37. Planta Med. v.68 Platycodin D and D3 increase airway mucin release in vivo and in vitro in rats and hamsters Shin,C.Y.;W.J.Lee;E.B.Lee;E.Y.Choi;K.H.Ko https://doi.org/10.1055/s-2002-23130
  38. Yakugaku Zasshi. v.92 Pharmacological studies on Platycodon grandiflorum A. DC. Takagi,K.;E.B.Lee
  39. Cell v.81 Yama/CPP32, a mammalian homolog of CED-3, is a CrmA-inhibitable protease that cleaves the death substrate poly(ADP-ribose) polymerase Tewari,M.;L.T.Quan;K.O'Rourke;S.Desnoyers;Z.Zeng;D.R.Beidler;G.G.Poirier;G.S.Salvesen;V.M.Dixit https://doi.org/10.1016/0092-8674(95)90541-3

피인용 문헌

  1. Effects of Cheongpyesagan-tang and YKK012 on in vitro and in vivo Colon Cancer Cell Growth with and without CPT-11 vol.30, pp.1, 2015, https://doi.org/10.6116/kjh.2015.30.1.33.
  2. The Hypocholesterolemic Effect of Platycodi radix Saponin in Rats Fed a Hypercholesterol Diet vol.24, pp.1, 2013, https://doi.org/10.7856/kjcls.2013.24.1.141