PMID: 8599864Jan 1, 1996Paper

Cell-cycle arrest and p53 accumulation induced by geldanamycin in human ovarian tumour cells

Cancer Chemotherapy and Pharmacology
A J McIlwrathR Brown

Abstract

We have analysed the cell-cycle arrests and cytotoxicity of the A2780 human ovarian cell line in response to geldanamycin, a benzoquinoid ansamycin that can inhibit tyrosine kinases. Geldanamycin causes a dose-dependent G2 arrest and reversible inhibition of entry into the S phase in A2780 cells. After a 3-h exposure to 0.1 microM geldanamycin, the cells show an increase in accumulation of p53 protein that is maximal at 24 h after drug exposure. Increased p53 levels can be induced in cells by DNA-damaging agents; however, using alkaline elution and sister chromatid exchange assays we detect no DNA damage induced by geldanamycin. Using dominant negative mutant TP53 transfectants of A2780 we have analysed the possible dependence of geldanamycin-induced cell-cycle arrests on the presence of functional p53. We observe no difference in cell-cycle arrests in mutant p53 transfectants known to have the p53-DNA damage-response pathway inactivated as compared with vector-alone controls. Similarly, we observe no difference in clonogenic resistance to the cytotoxicity of geldanamycin in these cells. These results suggest that geldanamycin can induce increased p53 protein by a mechanism not involving DNA damage. Furthermore, the cell-cycle ...Continue Reading

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Citations

Nov 26, 2009·Acta Neuropathologica·Anna C NavisWiljan J A J Hendriks
Jul 27, 2011·Proceedings of the National Academy of Sciences of the United States of America·Lisa PhamEric D Kolaczyk
Jul 23, 2004·Anti-cancer Drugs·Jason Beliakoff, Luke Whitesell
Dec 24, 2010·Drug Metabolism and Disposition : the Biological Fate of Chemicals·Nan ZhengDuxin Sun
Jan 5, 2002·Expert Opinion on Biological Therapy·Alison Maloney, Paul Workman
May 25, 2010·Experimental Eye Research·Wen-Chuan WuYing-Hsien Kao
May 22, 2003·The American Journal of Pathology·George G ChenArthur K C Li
Sep 28, 2001·The Journal of Biological Chemistry·K F WinklhoferJ Tatzelt
Mar 10, 2001·International Journal of Gynecological Cancer : Official Journal of the International Gynecological Cancer Society·S. B. Kaye
Sep 22, 2005·Nature Reviews. Cancer·Luke Whitesell, Susan L Lindquist
Jul 4, 2002·The Journal of Eukaryotic Microbiology·J FrankelP J Keeling
Aug 10, 2019·Chemical Research in Toxicology·J Christopher CortonCarole L Yauk

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