idarubicin-induced DNA拓扑异构酶ⅱ可分裂的复合物的形成和长寿在人类白血病K562细胞。

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威尔莫E, F埃林顿,蒂尔乔丹,奥斯丁CA

idarubicin-induced DNA拓扑异构酶ⅱ可分裂的复合物的形成和长寿在人类白血病K562细胞。

生物化学杂志。2002年5月15日,63(10):1807 - 15所示。

PubMed ID

12034365 (在PubMed

]

文摘

Idarubicin (IDA)是一种蒽环霉素用于治疗急性骨髓性白血病(AML)是临床上重要的因为它的效力和亲油性(相比相关化合物道诺霉素和阿霉素)。这些药物目标DNA拓扑异构酶ⅱ(威尼斯平底渔船II),核酶,调节DNA拓扑。威尼斯平底渔船II中毒导致捕获酶的一个中间的周期称为“可分裂的复杂。”This study aims to increase understanding of drug interactions by use of the "TARDIS" (trapped in agarose DNA immunostaining) assay to measure drug-induced topo II cleavable complexes in individual cells treated with anthracyclines. Mammalian cells contain two isoforms of topo II (alpha and beta) and the TARDIS assay enables visualisation of isoform-specific complexes. Drug-treated cells were embedded in agarose, lysed and incubated with anti-topo II antibodies to microscopically detect topo IIalpha or beta complexes. Results for K562 cells (at clinically relevant concentrations) showed that IDA and idarubicinol, its metabolite, formed mainly topo IIalpha cleavable complexes, the level of which decreases at doses > 1 microM for IDA. Our data suggest that this decrease is due to catalytic inhibition by IDA at these doses. Doxorubicin formed low levels of topo IIalpha complexes and negligible topo IIbeta complexes. In cytotoxicity studies, IDA and idarubicinol were equipotent, but both were more potent than daunorubicin and doxorubicin. We showed for the first time that there was a persistent increase in levels of topo IIalpha cleavable complexes after removal of IDA, suggesting that its greater effectiveness may be associated with both the longevity and high levels of these complexes.

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药物靶点

药物	目标	类	生物	药理作用	行动
Idarubicin	DNA拓扑异构酶2α	蛋白质	人类	是的	抑制剂	细节