Epothilone induced cytotoxicity is dependent on p53 status in prostate cells

The Prostate
Margarita L IoffeRobert S DiPaola

Abstract

Epothilones are a promising class of drugs in clinical trials of prostate cancer that target the microtubules, similar to taxanes, and induce apoptosis in taxane resistant tumors. The tumor suppressor p53 is one important molecular mechanism of chemotherapy resistance that in some studies predicted tumor sensitivity to paclitaxel. We hypothesized that epothilone induced cytotoxicity would be influenced by the status of p53 in prostate cells. LNCaP, DU145, and a transformed rat prostate (RP) epithelial cell line with a temperature sensitive mutant p53 (val 135) were studied for the effect of epothilone on cell viability, cell cycle, and cell cycle checkpoint proteins. Epothilone had greater cytotoxicity in p53 mutant cancer cells compared to wild type cells. We confirmed our findings by creating a transformed RP epithelial cell line with a temperature sensitive mutant p53 (val 135). Using a tetrazolium (MTT) assay we found that epothilone (100 nM) decreased cell viability in RP cells by 90% with mutant p53 compared to 45% with wild type p53 (P < 0.01). Epothilone induced G2/M arrest in 50% of cells with mutant p53 compared to 25% with wild type p53 (P < 0.01). To begin to understand mechanism of epothilone induced G2/M arrest, w...Continue Reading

References

Jan 1, 1993·The Prostate·A G CarrollE P Gelmann
Jul 21, 1998·The Journal of Biological Chemistry·Y H LingR Perez-Soler
Jun 13, 2003·Seminars in Oncology·John RothermelJohn Hohneker
Sep 25, 2003·Annals of Oncology : Official Journal of the European Society for Medical Oncology·O SmaletzW K Kelly

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Citations

May 12, 2005·Urology·Robert S Dipaola, Ian M Thompson
Dec 18, 2008·Annals of Oncology : Official Journal of the European Society for Medical Oncology·A HussainA R Johri
Apr 8, 2006·American Journal of Clinical Oncology·Guru Sonpavde, Thomas E Hutson
Dec 18, 2007·Neoplasia : an International Journal for Oncology Research·Fatouma AlimirahDivaker Choubey
Jul 24, 2007·The Journal of Urology·Paul Mathew, Robert Dipaola
Aug 21, 2013·Cell Biology International·Aneta RogalskaAgnieszka Marczak
Feb 7, 2006·Cancer Treatment Reviews·Guru SonpavdeWilliam R Berry
Mar 1, 2005·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Matthew D GalskyW Kevin Kelly
Sep 17, 2005·Cancer Research·Balakrishnan RamanathanYeong-Shiau Pu

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