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Yasuaki Fukuda,Masahiro Kanbe,Manami Watanabe,Katsuaki Dan,Keiichi Matsuzaki,Susumu Kitanaka,Shohei Miyata 대한약학회 2013 Archives of Pharmacal Research Vol.36 No.8
We have previously reported that many ingenolcompounds derived from Euphorbia kansui exhibit topoisomerase(topo) II inhibitory activity. Of these compounds,3EZ,20Ac-ingenol inhibited topo I activity. Camptothecin,which inhibits the religation activity of topo I withoutinterfering with the binding of topo I to DNA and inducestopo I-mediated DNA cleavage, was used as a positivecontrol. In this study, we found that 3EZ,20Ac-ingenol didnot hamper the binding of topo I to DNA in the samemanner as camptothecin but affected the inhibition ofcleavage of one DNA strand. 3EZ,20Ac-ingenol inhibitedcell proliferation by blocking cell cycle progression in theG2/M phase. To define the mechanism of inhibition ofDT40 cell proliferation, the change in Akt activity wasobserved because Akt activity is regulated in response toDNA damage. Western blot analysis revealed that3EZ,20Ac-ingenol downregulated the expression of p-Akt,and apoptosis was detected by the presence of DNA double-strand breaks and caspase 3 activation.