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Cytotoxic Effects of Decursin from Angelica gigas Nakai in Human Cancer Cells

당귀로부터 정제한 Decursin의 인체암세포주에 대한 세포독성

  • Park, Kyung-Wuk (Dept. of Food Nutrition, Sunchon National University) ;
  • Choi, Sa-Ra (Dept. of Food Nutrition, Sunchon National University) ;
  • Shon, Mi-Yae (Dept. of Food Nutrition, Gyeongsang National University) ;
  • Jeong, Il-Yun (Radiation Application Research Division, Korea Atomic Energy Research Institute) ;
  • Kang, Kap-Suk (Dept. of Culinary Arts, Busan College of Information Technology) ;
  • Lee, Sung-Tae (Dept. of Biology, Sunchon National University) ;
  • Shim, Ki-Hwan (Division of Applied Life Sciences, Graduate School, Gyeongsang National University) ;
  • Seo, Kwon-Il (Dept. of Food Nutrition, Sunchon National University)
  • 박경욱 (순천대학교 식품영양학과) ;
  • 최사라 (순천대학교 식품영양학과) ;
  • 손미예 (경상대학교 식품영양학과) ;
  • 정일윤 (한국원자력연구소 방사선식품생명공학연구팀) ;
  • 강갑석 (부산정보대학 호텔조리과) ;
  • 이성태 (순천대학교 생물학과) ;
  • 심기환 (경상대학교 대학원 응용생명과학부) ;
  • 서권일 (순천대학교 식품영양학과)
  • Published : 2007.11.30

Abstract

Anticarcinogenic-active compound was isolated and purified from Angelica gigas Nakai. The compound was identified as decursin ($C_{19}H_{20}O_5$; molecular weight 328) by mass, IR spectrophotometry $^1H-NMR$ and $^{13}C-NMR$. The proliferation decreased in a dose dependant fashion in the MCF-7 cells treated with decursin for 24 hours over the concentration of $20{\mu}g/mL$. The $IC_{50}$ value of the decursin treatment for 24 hours were 31.04, 33.60, 27,24, $20.45{\mu}g/mL$ in the SW480, 293, HepG2 and MCF-7 cells, respectively, The growth inhibitory effect was stronger in the MCF-7 cells compared to other cells including 293 of human normal cells. The chromatin condensation, apoptotic body formation and DNA fragmentation were examined in the cells treated with decursin. These results suggest that decursin from Angelica gigas Nakai inhibited the growth through apoptosis in MCF-7 cells.

당귀로부터 항암활성을 화합물을 silicagel column chromatography를 이용하여 분리 및 정제한 후, $^1H$$^{13}C-NMR$ MS, HMQC 및 COSY spectrum(500 MHz $CDCl_3$) 분석을 통하여 분자량 328의 decursin임을 구조 동정하였다. 정제된 decursin을 MCF-7에 24시간 처리한 결과 $20{\mu}g/mL$ 이상에서 농도 의존적으로 암세포주의 성장을 억제하였으며, SW480, HepG2, MCF-7및 293과 같은 인체 암세포주에 대한 decurcin의 $IC_{50}$값은 각각 31.04, 27.24, 20.45 및 $33.60{\mu}g/mL$로 나타나, decursin은 인체 정상세포주인 293세포를 포함한 다른 세포에 비하여 MCF-7에 대하여 가장 높은 성장억제 활성을 보여주었다. MCF-7세포에 decursin을 처리한 결과 대조군에서 균일한 핵의 형태가 관찰된 것에 반해 처리군의 경우는 핵의 응축과 apoptotic body를 보였고, DNA 절편이 관찰되었다. 이 결과는 당귀에서 분리한 decursin은 MCF-7세포에서 apoptosis를 통하여 세포의 성장을 억제하는 것을 암시한다.

Keywords

References

  1. Ko KS, Kim YS. 1991. An illustrated book of the Korean flora. Academy Publishing Co, Korea. p 433-434
  2. Lee SL. 1994. Phytology. Youngm Lim Publishing Co., Seoul. p 578-580
  3. Ahn KS. 1996. A study on the anticancer and immunostimulating agents from the root of Angelica gigas Nakai. PhD Dissertation. Korea University
  4. Kang YG, Lee JH, Chae HJ, Kim DH, Lee SH, Park SY.2003. HPLC analysis and extraction methods of decursin and decursinol angelate in Angelica gigas root. Kor J Pharmacogn 34: 201-205
  5. Ryu KS, Hong ND, Kim NJ, Kong YY. 1990. Studies on the coumarin constituents of the root of Angelica gigas Nakai. Isolation of decursinol angelate and assay of decursinol angelate and decursin. Kor J Phymacogn 21: 64-68
  6. Chi HJ, Kim HS. 1988. Studies on essential oil of plants of angelica genus in Korea (Ⅰ) essential oils of Angelica gigantis radix. Kor J Pharmacogn 19: 239-247
  7. 이순우, 윤미혜, 최옥경, 윤덕희, 김범호. 1992. 당귀성분 중 Decursin의 HPLC 분석법 산지별 함량비교에 관한 연구. 경기도보건환경원보 5: 35
  8. Ryu KS, Hong ND, Kim NJ, Kong YY. 1990. Studies on the coumarin constituents of the root of Angelica gigas Nakai isolation of decursinol angelate and assay of decursinol angelate and decursin. Korean J Phamacogn 21: 64-68
  9. Woo WS, Shin KH, Ryu KS. 1982. Annual report of natural products research institute. Seoul National University, Korea. p 59-64
  10. Kim HS, Park HJ, Chi HJ. 1980. A study of effects of the root components of Angelica gigas. Korean J Pharmacogn 11: 11-14
  11. Ahn KS, Sim WS, Kim IH. 1996. A cytotoxic agent and protein kinase C activator from the root of Angelica gigas. Planta Med 62: 7-9 https://doi.org/10.1055/s-2006-957785
  12. Han SB, Kim YH, Lee CW, Park SM, Lee HY, Ahn KS, Kim IH, Kim HM. 1998. Charateristic immunostimulation by angelan isolated from Angelica gigas Nakai. Immunopharmacol 40: 39-48 https://doi.org/10.1016/S0162-3109(98)00026-5
  13. Wn H, Kong L, Wu M, Xi P. 1996. Effects of different processed products of radix Angelica sinensis on clearing out oxygen free radicals and anti-lipid peroxidation. Chung Kuo ChungYoo Tsa Chin 21: 599-601
  14. Salikhova RA, Poroshenko GG. 1995. Antimutagenic properties of Angelica archangelica L. Vestn Ross Akad Med Nauk 1: 58-61
  15. Yim D, Singh RP, Agarwal C, Lee S, Chi H, Agarwal R. 2005. A novel anticancer agents, decursin, induces G1 arrest and apoptosis in human prostate carcinoma cells. Cancer Res 65: 1035-1044
  16. Kim HH, Ahn KS, Han H, Choung SY, Choi SY, Kim IH. 2005. Decursin and PDBu; two PKC activators distinctively acting in the megakaryocytic differentiation of K562 human erythroleukemia cells. Leukemia Res: 1407-1413 https://doi.org/10.1016/j.leukres.2005.05.001
  17. Kim HH, Bang SS, Choi JS, Han HG, Kim IH. 2005. Involvement of PKC and ROS in the cytotoxic mechanism of anti-leukemic decursin and its derivatives and their structure-activity relationship in human K562 erythroleukemia and U937 myeloleukemia cells. Cancer Lett 223: 191-201 https://doi.org/10.1016/j.canlet.2004.10.025
  18. 통계청. 1996. 사망원인 통계연보
  19. Wynder EL, Gori GB. 1977. Contribution of enviroment to cancer medicine. J Nati Cancer Inat 58: 826-832
  20. Miyazaki T, Nishijma M. 1981. Strutural examination of a water soluble antitumor polysaccaride of Ganoderma incidum. Chem Pharm Bull 29: 3611-3616 https://doi.org/10.1248/cpb.29.3611
  21. Hong MH. 1972. Statistical studies on the formularies of oriental medicine (Ⅰ). prescription frequency and their origin distribution of herb drugs. Kor J Pharmacogn 3: 57-64
  22. Cha SM. 1977. Potential anticancer medicinal plants. A statistical evaluation of their frequencies of appearance in oriental medicine formularies. Kor J Pharmacogn 8: 1-15
  23. Lee SH, Lee YS, Jung SH, Shin KH, Kim BK, Kang SS. 2003. Antioxidant activities of decursinol angelate and decursin from Angelica gigas roots. Nat Prod Sci 9: 170-173
  24. Ahn KS, Sim WS, Kim IH. 1995. Decursin: a cytotoxic agent and protein kinase C activator from the root of Angelica gigas. Planta Med 62: 7-9 https://doi.org/10.1055/s-2006-957785
  25. Chen IS, Chang CT, Sheen WS, Tsai LL, Teng CM, Duh CY, Ko FN. 1996. Coumarins and antiplatelet aggregation constituents from formosan Pseucedanum japonicum. Phytochem 41: 525-530 https://doi.org/10.1016/0031-9422(95)00625-7
  26. Rho SB, Han EJ, Bae SJ. 2000. Effects of quinone reductase induction and cytotoxicity of the Angelica radix extracts. J Korean Soc Food Sci Nutr 29: 147-152

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