PMID: 11918672Mar 29, 2002Paper

ICRF-193, a catalytic inhibitor of DNA topoisomerase II, inhibits re-entry into the cell division cycle from quiescent state in mammalian cells

Genes to Cells : Devoted to Molecular & Cellular Mechanisms
Muktadir S HossainKazuhisa Sekimizu

Abstract

To describe the requirement of DNA topoisomerase II (topo II) during transition from the quiescent state (G0 phase) to the cell division cycle in mammalian cells, we examined the influence of ICRF-193, a catalytic inhibitor of topo II, on re-entry into the cell division cycle of quiescent cells in response to appropriate growth stimuli. The re-entry into the S phase of cultured cell lines arrested at the quiescent (G0) phase by serum-starvation was sensitive to 10 microm ICRF-193. DNA syntheses induced by lipopolysaccharide in murine spleen cells or by release from contact-inhibition were also inhibited by ICRF-193. The cell lines with a high-level of resistance toward ICRF-193 due to a point mutation in the topo IIalpha gene entered into the S phase from quiescence in the presence of ICRF-193. The drug did not inhibit entry into the S phase in cultured cells released from arrest at the metaphase or G1 phase. There is an ICRF-193-sensitive step during re-entry of quiescent mammalian cells into the cell division cycle upon growth stimulation and the drug targets topo IIalpha during the process.

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Citations

Sep 23, 2014·European Journal of Medicinal Chemistry·Wang ChenYuemao Shen
Aug 24, 2007·Expert Opinion on Investigational Drugs·Maximilian Peters, Natalya M Kogan
Oct 6, 2004·Genes to Cells : Devoted to Molecular & Cellular Mechanisms·Muktadir S HossainKazuhisa Sekimizu
Mar 26, 2003·Genes to Cells : Devoted to Molecular & Cellular Mechanisms·Nobuyoshi AkimitsuKazuhisa Sekimizu
Jun 1, 2012·The Journal of Immunology : Official Journal of the American Association of Immunologists·Takao SudoYuzuru Kanakura
Nov 2, 2019·Genes·Joyce H Lee, James M Berger

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