Effect of 4β-Arylamino Derivatives of 4′-O-Demethylepipodophyllotoxin on Human DNA Topoisomerase II, Tubulin Polymerization, KB Cells, and Their Resistant Variants

Jang Yang Chang, Fu Sheng Han, Su Ying Liu, Zhe Qing Wang, Kuo Hsiung Lee, Yung Chi Cheng

研究成果: Article同行評審

47 引文 斯高帕斯(Scopus)

摘要

Six 4β-arylamino derivatives of 4′-O-demethylepipodophyllotoxin were examined for inhibitory activity against human DNA topoisomerase II and tubulin polymerization, their ability to generate protein-linked DNA breaks in cells, and their cytotoxicity toward the KB cell line and its VP-16- and vincristine-resistant variants. Five of these derivatives were 5- to 10-fold more potent than VP-16 as inhibitors of DNA topoisomerase II in vitro, and all of these derivatives could generate the same amount of or more protein-linked DNA breaks in cells than VP-16 at 1–20 μm. Tubulin polymerization was inhibited by these compounds to different degrees in the order: podophyllotoxin ≻ W73 ≻ W87 ≻ NPF ≻ NPC ≻ W68 ≻ W38 >≻VP-16. These analogues were cytotoxic not only to KB cells but also to their VP-16-resistant and vincristine-resistant variants which showed decreased cellular uptake of VP-16 and a decrease in DNA topoisomerase II content or overexpression of MDR1 phenotype. These characteristics may cause these derivatives to have different spec-trums of antitumor activity.

原文English
頁(從 - 到)1755-1759
頁數5
期刊Cancer Research
51
發行號7
出版狀態Published - 1991 4月 1

All Science Journal Classification (ASJC) codes

  • 腫瘤科
  • 癌症研究

指紋

深入研究「Effect of 4β-Arylamino Derivatives of 4′-O-Demethylepipodophyllotoxin on Human DNA Topoisomerase II, Tubulin Polymerization, KB Cells, and Their Resistant Variants」主題。共同形成了獨特的指紋。

引用此