DNA topoisomerases as targets of anticancer drugs

H. F. Shang, T. L. Chen, C. P. Lin, J. Hwang

研究成果: 雜誌貢獻文章

摘要

Eukaryotic DNA topoisomerases are ubiquitous nuclear enzymes that alter DNA topology by breaking and rejoining DNA strands. There are two classes of DNA topoisomerases; DNA topoisomerase I introduces a transient single-strand DNA break, while topoisomerase II introduces transient double-strand DNA breaks for each catalytic reaction. Both are important for solving topological problems arising during DNA replication, transcription, recombination and other cellular functions. Recently, scientists have realized the importance of topoisomerases as new therapeutic targets for antibacterial, antifungal, antiparasitic, antiviral and anticancer drugs. The present review focuses on anticancer drugs targeting mammalian DNA topoisomerases, which are named DNA topoisomerase poison. Camptothecin and VM26 (teniposide) are representative DNA topoisomerase poisons that target DNA topoisomerase I and topoisomerase II, respectively. These drugs alter the breakage-reunion reactions of DNA topoisomerases by trapping topoisomerase-DNA cleavable complexes in both the purified system and cultured cells. However, resistance to various DNA topoisomerase poisons has been documented in cancer cells with repect to MDR1 overexpression, reduced topoisomerase levels, drug-resistant mutant topoisomerase, lengthened cell cycle time and altered DNA repair function. A better understanding of the molecular targets for anticancer drugs and the various drug-resistance mechanisms may help us to discover and tailor new drugs for particular drug-resistant tumors.

原文英語
頁(從 - 到)145-153
頁數9
期刊Journal of Food and Drug Analysis
3
發行號3
出版狀態已發佈 - 1995

ASJC Scopus subject areas

  • Food Science
  • Pharmacology

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  • 引用此

    Shang, H. F., Chen, T. L., Lin, C. P., & Hwang, J. (1995). DNA topoisomerases as targets of anticancer drugs. Journal of Food and Drug Analysis, 3(3), 145-153.