Cordyceps militaris로부터 분리한 Ergosterol Peroxide의 한국인 암세포주에 대한 항암작용

In vitro Antitumor Activity of Ergosterol Peroxide Isolated from Cordyceps militaris on Cancer Cell Lines from Korean Patients

  • 김하원 (서울시립대학교 생명과학과) ;
  • 김영호 (충남대학교 약학대학) ;
  • 채흥복 (충남대학교 약학대학) ;
  • 남경숙 (서울시립대학교 생명과학과) ;
  • 이승정 (서울시립대학교 생명과학과) ;
  • 안혜숙 (서울시립대학교 생명과학과) ;
  • 정은호 (서울시립대학교 생명과학과) ;
  • 윤승현 (서울시립대학교 생명과학과) ;
  • 성수경 (서울시립대학교 생명과학과) ;
  • 이성진 (서울시립대학교 생명과학과) ;
  • 현진원 (서울대학교 의과대학 약리학교실)
  • Kim, Ha-Won (Department of Life Science, University of Seoul) ;
  • Kim, Young-Ho (College of Pharmacy, Chung Nam National University) ;
  • Cai, Xing Fu (College of Pharmacy, Chung Nam National University) ;
  • Nam, Kyong-Suk (Department of Life Science, University of Seoul) ;
  • Lee, Seung-Jung (Department of Life Science, University of Seoul) ;
  • An, Hye-Suk (Department of Life Science, University of Seoul) ;
  • Jeong, Eun-Ho (Department of Life Science, University of Seoul) ;
  • Yun, Seung-Hyun (Department of Life Science, University of Seoul) ;
  • Sung, Su-Kyong (Department of Life Science, University of Seoul) ;
  • Lee, Sung-Jin (Department of Life Science, University of Seoul) ;
  • Hyun, Jin-Won (Department of Pharmacology, College of Medicine, Seoul National University)
  • 발행 : 2001.04.30

초록

곤충기생성 균류인 번데기동충하초는 각종 약리활성을 나타내는 것으로 유명하다. 국내에서 인공재배한 번데기동충하초 자실체를 n-hexane으로 추출하여 항암성분을 실리카젤 칼럼크로마토그래피로 순수하게 분리하여 $^1H-NMR$$^{13}C-NMR$로 그 구조를 밝혀본 결과 ergosterol peroxide $(5{\alpha},\;8{\alpha}-epidioxy-24(R)-methylcholesta-6,22-dien-3{\beta}-ol)$로 밝혀졌다. 분리한 crgosterol peroxide를 한국인의 암환자에서 분리한 각종 암세포에 대하여 항암작용을 측정한 결과, 3일 후에 위암세포주인 SNU-1 암세포에 대하여 가장 강한 항암작용을 나타내었다. 한국인의 암환자에서 유래한 위암세포인 SNU-1, 간암세포인 SNU-354 및 직장암세포인 SNU-C4 암세포 등에 대한 6일 후에 ergosterol peroxide의 50% 성장억제농도는 각각 75.8, 39.7, $32.7{\mu}g/ml$이었다. 따라서 ergosterol peroxide 성분은 번데기동충하초의 항암성분중의 하나로 밝혀졌다.

Entomopathogenic fungus of Cordyceps militaris is famous of its medicinal efficacies. An antitumor compound was purified from the n-hexane extract of artificially cultivated fruiting bodies of C. militaris and identified as ergosterol peroxide $(5{\alpha},\;8{\alpha}-epidioxy-24(R)-methylcholesta-6,22-dien-3{\beta}-o1,\; C_{28}H_{44}O_3)$ mainly by $^1H\;and\;^{13}C-NMR$ spectroscopic techniques. When the antitumor activity of ergosterol peroxide was measured against 3 tumor cell lines from Korean cancer patients, it showed the most strong activity against gastric cancer SNU-l cell line 3 days after treatment. The 50% inhibitory concentrations $(IC_{50})$ of ergosterol peroxide 6 days after treatment were $75.8{\mu}g/ml$ for human gastric SNU-1 tumor cell line, $39.7{\mu}g/ml$ for human colorectal SNU-C4 tumor cell line and $32.7{\mu}g/ml$ for human hepatoma SNU-354 cell line.

키워드

참고문헌

  1. 약학회지 v.43 백강잠의 세포독성 성분 권학철;문형인;최상훈;이정옥;조세연;정이연;김선여;이강노
  2. 健康を蘇らせる奇蹟の菌食-神秘の 冬蟲夏草 溝口勝
  3. 한국의 동충하초 성재모
  4. 한국균학회지 v.26 단백질 분석을 기초로한 Cordyceps속 동충하초의 분류 성재모;이현경;유영진;최영상;김상희;김용욱;성기호
  5. 한국균학회지 v.27 분리된 동충하초 균주를 이용한 자실체 생산 성재모;최영상;이현경;김상희;김용욱;성기호
  6. 생약학회지 v.31 눈꽃동충하초의 약물활성 심진영;이연실;임순성;신국현;현진이;김성연;이은방
  7. 日本冬蟲夏草があなたのガンを消すかもしれない 自然藥食微生物硏究所
  8. 한국균학회지 v.27 Cordyceps militaris 인공자실체 형성조건 최인영;최정식;이왕휴;유영진;정기태;주인옥;최영근
  9. J. Nat. Prod. v.49 Three new lanostanoids from Ganoderma lucidum Arisawa, M.;Fujita, A.;Saga, M.;Fukumura, H.;Hayashi, T.;Shimizu, M.;Morita, N.
  10. J. Biol. CHem. v.253 Cordycepin: an inhibitor of newly synthesized globin messenger RNA Beach, L.R.;Ross, J.
  11. Phytochem. v.51 Antitumor sterols from the mycelia of Cordyceps sinensis Bok, J.W.;Lermer, L.;Chilton, J.;Klingeman, H.G.;Towers, G.H.
  12. Zhongguo Kangshensu Zazhi v.21 NMR and IR studies on the characterization of cordycepin and 2'-deoxyadenosine Chen, S.Z.;Chu, J.Z.
  13. Biochim. Biophys. Acta. v.103 Incorporation of cordycepin (3'-deoxyadenosine) into ribonucleic acid and deoxyribonucleic acid of human tumor cells Cory, J.G.;Suhadolnik, R.J.;Resnick, B.;Rich, M.A.
  14. J. Chem. Soc. Cordycepin, a metabolic product from cultures of Cordycepin militaris (Linn.) Link. Part I. isolation and characterisation Cunningham, B.K.G.;Hutchinson, S.A.;Manson, W.;Spring, F.S.
  15. Chem. Pharm. Bull. (Tokyo) v.42 Isolation and characterization of immunosuppressive components of three mushrooms, Pisolithus tinctorius, Microporus flabelliformis and Lenzites betulina Fujimoto, H.;Nakayama, M.;Nakayama, Y.;Yamazaki, M.
  16. Biochem. Biophys. Res. Commun. v.14 Identification of cordycepin, a metabolite of Cordyceps militaris, as 3'-deoxyadenosine Kaczka, E.A.;Trenner, N.R.;Arison, B.;Walker, R.W.;Folkers, K.
  17. Arch. Pharm. Res. v.20 Anticomplementary activity of ergosterol peroxide from Naematoloma fasciculare and reassignment of NMR data Kim, D.S.;Baek, N.I.;Oh, S.R.;Jung, K.Y.;Lee, I.S.;Kim, J.H.;Lee, H.K.
  18. Zentralbl Mikrobiol. v.145 Distribution, ecology, and immunosuppressive properties of Tricholoma populinum (Basidiomycetes) Kreisel, H.;Lindequist, U.;Horak, M.
  19. Biochim. Biophys. Acta. v.740 The effect of poly(A) segment size on the inhibition of hnRNA biosynthesis by cordycepin in rat brain cells Kuznetsov, D.A.;Musaev, N.I.;Khasigov, P.Z.;Nikolaev, A.Y.
  20. Pharmazie v.44 Isolation, characterization and structure elucidation of a substance with immunosuppressive action from Tricholoma populinum Lange Lindequist, U.;Teuscher, E.;Wolf, B.;Volsgen, A.;Hoffmann, S.;Kutschabsky, L.;Franke, P.;Seefeldt, R.
  21. Pharmazie v.44 The antiviral action of ergosterol peroxide Lindequist, U.;Lesnau, A.;Teuscher, E.;Pilgrim, H.
  22. Nature Medicine (Tokyo) v.52 Screening of anti-HIV-1 activity of north american plants. Anti-HIV-1 activities of plant extracts, and active components of Lethalia vulpina (L.) Hue Nakanishi, T.;Murata, H.;Inatomi, Y.;Inada, A.;Murata, J.;Lang, F.A.;Yamasaki, K.;Nakano, M.;Kawahata, T.;Mori, H.;Otake, T.
  23. Int. J. Cancer v.62 Characterization of cell lines established from human hepatocellular carcinoma Park, J.G.;Lee, J.H.;Kang, M.S.;Park, K.J.;Jeon, Y.M.;Lee, H.J.;Kwon, H.S.;Park, H.S.;Yeo, K.S.;Lee, K.U.;Kim, S.T.;Chung, J.K.;Hwang, Y.J.;Lee, H.S.;Kim, C.Y.;Lee, Y.I.;Chen, T.R.;Hay, R.J.;Song, S.Y.;Kim, W.H.;Kim, C.W.;Kim, Y.I.
  24. J. Natl. Cancer Inst. v.86 MDR1 gene expression: its effect on drug resistance to doxorubicin in human hepatocellular carcinoma cell lines Park, J.G.;Lee, S.K.;Hong, I.G.;Kim, H.S.;Lim, K.H.;Choe, K.J.;Kim, W.H.;Kim, Y.I.;Tsuruo, T.;Gottesman, M.M.
  25. Biochem. Syst. Ecol. v.27 The chemistry of Bacidia stipata (Lichens, Ascomycotina) Piovano, M.;Guzman, G.;Garbarino, J.A.;Chamy, M.C.
  26. Int. J. Cancer v.15 Effect of cordycepin on the replication of type-c RNA tumor viruses Richardson, L.S.;Ting, R.C.;Gallo, R.C.;Wu, A.M.
  27. J. Cell. Biol. v.41 The selective interruption of nucleolar RNA synthesis in HeLa cells by cordycepin Siev, M.;Weinberg, R.;Penman, S.
  28. Biol. Pharm. Bull. v.19 Inhibitory effects of sterols isolated from Chlorella vulgaris on 12-Q-tetradecanoylphorbol-13-acetate-induced inflammation and tumor promotion in mouse skin Yasukawa, K.;Akihisa, T.;Kanno, H.;Kaminaga, T.;Izumida, M.;Sakoh, T.;Tamura, T.;Takido, M.