Chivosazole F, An Efficient Inhibitor of Multidrug-Resistant Cancer Cells Isolated from Sorangium Cellulosum [Myxobacteria]

Chivosazole F: 점액세균 Sorangium Cellulosum이 생산하는 다제내성 암세포의 생장억제물질

  • Ahn Jong-Woong (Division of Marine Environment & Bioscience, Korea Maritime University) ;
  • Choi Sang-Un (Medicinal Science Division, Korea Research Institute of Chemical Technology) ;
  • Seo Youngwan (Division of Marine Environment & Bioscience, Korea Maritime University) ;
  • Rho Jung-Rae (Department of Marine Information Science, Kunsan National University)
  • 안종웅 (한국해양대학교 해양환경생명과학부) ;
  • 최상운 (한국화학연구원 생명의학연구부) ;
  • 서영완 (한국해양대학교 해양환경생명과학부) ;
  • 노정래 (군산대학교 해양학과)
  • Published : 2005.10.01

Abstract

In the course of our search for compounds effective to multidrug-resistant cancer cells from myxobacteria with the adriamycin-resistant cancer cell line CL02, we found cytotoxic activity against the CL02 cells in culture extract of Sorangium cellulosum JW1045. Activity-guided fractionation of the culture extract led to the isolation of an active principle, chivosazole F, This compound showed high cytotoxic activity against cultured human cancer cells. The $IC_{50}$ values, measured by a SRB assay with different cell lines, ranged from 0.1 to 10 ng/ml. Furthermore chivosazole F was as active against drug-resistant cancer cells CL02 and CP70 as against the corresponding sensitive cells.

암세포가 특정 항암제에 의해 내성을 획득하면 구조가 상이한 타 항암제에도 교차내성을 나타내는 이른바 암세포의 다약제내성(MDR)이 암 화학요법에 있어서 가장 심각한 문제가 되고 있다. 본 연구에서는 점액세균의 대사산물로부터 다약제내성 암세포에 대한 생장억제물질을 탐색하는 과정에서 cellulose 용해성 점액세균인 Sorangium cellulosum Jw1045의 대사산물에서 우수한 활성을 발견하고 그 활성본체로서 polyene-macrolide계 화합물인 chivosazole F를 분리하였다. Chivosazole F는 시험한 인체기원의 암세포에 대해 모두 강한 생장억제작용을 나타내었으며 $(IC_{50}=0.1\~10ng/ml)$, 다약제내성 암세포주인 CL02와 CP70에 대해서도 감수성세포주와 동일한 활성을 나타내었다. 이러한 사실은 chivosazole F가 암세포에 대해 다제내성을 유도하지 않는 우수한 활성물질임을 나타탬과 동시에 다제내성을 극복하는 신규 항암제 선도화합물로서의 유용성을 시사하는 것으로 그 의미가 크다.

Keywords

References

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