Applied Biological Chemistry

The Korean Society for Applied Biological Chemistry (한국응용생명화학회)
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in vitro Anticancer Activity and in vivo Chronic Toxicity of Homoharringtonine

개비자나무 유효성분인 homoharringtonine의 in vitro 항암활성 및 in vivo 만성 독성

  • Yoo, Gui-Jae (Department of Food and Biotechnology, and Center for Food Function and Safety, Hoseo University) ;
  • Cho, Chul-Hee (Department of Food and Biotechnology, and Center for Food Function and Safety, Hoseo University) ;
  • Lee, Gun-Soon (Departmant of Living Sciences, Korea National Agricultural Collage) ;
  • Ryoo, Zae-Young (School of Life Science and Biotechnology, Kyung Pook National University) ;
  • Chae, Hee-Jeong (Department of Food and Biotechnology, and Center for Food Function and Safety, Hoseo University)
  • 유귀재 (호서대학교 식품생물공학과 및 식품기능안전연구센터) ;
  • 조철희 (호서대학교 식품생물공학과 및 식품기능안전연구센터) ;
  • 이건순 (한국농업대학 교양공통학부) ;
  • 류재웅 (경북대학교 자연과학대학 생명공학부) ;
  • 채희정 (호서대학교 식품생물공학과 및 식품기능안전연구센터)
  • Published : 2008.06.30
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Abstract

Cell proliferation inhibitory effects of homoharringtonine (HHT), an active drug substance in Cephalotaxus koreana, against blood cancer cell line K562 were evaluated. In addition, in vivo chronic toxicity test with mouse was carried out. When K562 cell line was treated everyday for 9, 6, 3 days, $IC_{50}$ values of HHT were determined as 0.27, 0.37, and 1.10 mM respectively. The anticancer activity of HHT was comparable to adriamycin, a known anticancer drug compound for blood cancer treatment. in vivo chronic toxicity test of the HHT, the number of red blood cell (RBC) showed no significant difference. From the analysis of the liver-functional enzymes in blood, all of liver damage related enzymes such as glutamate-oxalate-transferase (GOT), glutamate-pyruvate-transferase (GPT), cholesterol (Chol) and alkaline phosphatase (ALP) showed no significant change. However, from the histologic test, a neutrophil of the band type in liver tissue was observed.

개비자나무의 유효성분으로 알려진 homoharringtonine의 암세포주 K562에 대한 세포증식 저해 활성을 분석하였고, 마우스를 이용한 만성독성시험을 수행하였다. 총 약물처리 시간에 따른 최적 투여조건 결정 실험에서는 HHT를 9일, 6일, 3일 동안 매일 처리할 경우 각각 0.27, 0.37, 1.10mM의 농도에서 K562세포의 성장을 50% 감소시킴을 확인하였다. 기존 백혈병 치료제로 사용되고 있는 adriamycin과의 비교실험 결과 HHT는 K562 세포주에 대하여 adriamycin보다 낮은 저해율을 나타냈으나 비교적 근사한 값을 가졌다. HHT의 만성독성 실험 결과 혈액학적 지표 측정 실험에서 적혈구수(RBC)는 대조군과 HHT 투여군 사이에 유의적인 차이가 없었고, 간 기능 관련 효소의 혈액을 분석한 결과, 간 손상과 관련된 효소glutamate-oxalate-transferase, glutamate-pyruvate- transferase, cholesterol 및 alkaline phosphatase 모두 정상 범위에 있었다. 그러나 간 조직학적 검사에서는 HHT를 투여한 마우스의 간 조직에서 밴드형의 호중구를 침착시키는 것이 확인되었다.

Keywords

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