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

Research output: Contribution to journalArticle

46 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)1755-1759
Number of pages5
JournalCancer Research
Volume51
Issue number7
Publication statusPublished - 1991 Apr 1

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

Fingerprint Dive into the research topics of 'Effect of 4β-Arylamino Derivatives of 4′-O-Demethylepipodophyllotoxin on Human DNA Topoisomerase II, Tubulin Polymerization, KB Cells, and Their Resistant Variants'. Together they form a unique fingerprint.

  • Cite this