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The Cytotoxic and Anti-proliferative Effects of 3-Hydrogenkwadaphnin in K562 and Jurkat Cells Is Reduced by Guanosine
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  • The Cytotoxic and Anti-proliferative Effects of 3-Hydrogenkwadaphnin in K562 and Jurkat Cells Is Reduced by Guanosine
  • The Cytotoxic and Anti-proliferative Effects of 3-Hydrogenkwadaphnin in K562 and Jurkat Cells Is Reduced by Guanosine
저자명
Moosavi. Mohammad Amin,Yazdanparast. Razieh,Sanati. Mohammad Hasan
간행물명
Journal of biochemistry and molecular biology
권/호정보
2005년|38권 4호|pp.391-398 (8 pages)
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생화학분자생물학회
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정기간행물|ENG|
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이 논문은 한국과학기술정보연구원과 논문 연계를 통해 무료로 제공되는 원문입니다.
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기타언어초록

3-hydrogenwadaphnin (3-HK) is a new daphnane-type diterpene ester isolated from Dendrostellera lessertii with strong anti-tumoral activity in animal models and in cultures. Here, prolonged effects of this new agent on proliferation and viability of several different cancerous cell lines were evaluated. Using [$^3H$]thymidine incorporation, it was found that the drug inhibited cell proliferation and induced G1/S cell cycle arrest in leukemic cells 24 h after a single dose treatment. The cell viability of Jurkat cells was also decreased by almost 10%, 31% and 40% after a single dose treatment (7.5 nM) at 24, 48 and 72 h, respectively. The drug-treated cells were stained with acridine orange/ethidium bromide to document the chromatin condensation and DNA fragmentation. These observations were further confirmed by detection of DNA laddering pattern in the agarose gel electrophoresis of the extracted DNA from the treated cells. Treatment of K562 cells with the drug at 7.5, 15 and 30 nM caused apoptosis in 25%, 45% and 65% of the cells, respectively. Exogenous addition of $25-50;{mu}M$ guanosine and/or deoxyguanosine to the cell culture of the drug-treated cells restored DNA synthesis, released cell arrest at G1/S checkpoint and decreased the apoptotic cell death caused by the drug. These observations were not made using adenosine. However, the drug effects on K562 cells were potentiated by hypoxanthine. Based on these observations, perturbation of GTP metabolism is considered as one of the main reasons for apoptotic cell death by 3-HK.