Anja-Martina Rottach1, Hannes Ahrend1, Benedikt Martin1, Reinhard Walther2, Uwe Zimmermann1, Martin Burchardt1, Matthias B Stope3. 1. Department of Urology, University Medicine Greifswald, Ferdinand-Sauerbruch-Straße, 17475, Greifswald, Germany. 2. Department of Medical Biochemistry and Molecular Biology, University Medicine Greifswald, Ferdinand-Sauerbruch-Straße, 17475, Greifswald, Germany. 3. Department of Urology, University Medicine Greifswald, Ferdinand-Sauerbruch-Straße, 17475, Greifswald, Germany. matthias.stope@uni-greifswald.de.
Abstract
PURPOSE: Cabazitaxel, a semi-synthetic taxane of the third generation, inhibits prostate cancer (PC) cell growth by affecting the microtubule architecture. Since cabazitaxel has also been demonstrated to inhibit androgen receptor (AR) functionality, AR and AR-associated heat shock protein (HSP) expressions in the presence of cabazitaxel were characterized. METHODS: AR and HSP expressions were assessed via Western blotting utilizing a PC-cell-line in vitro system incubated with cabazitaxel. RESULTS: Incubation experiments with 0.3 nM cabazitaxel exhibited significantly reduced levels of AR and the AR-associated factors HSP90α, HSP40, and HSP70/HSP90 organising protein. Furthermore, expression of the anti-apoptotic factor HSP60 was suppressed. In contrast to other anticancer compounds, cabazitaxel did not alter the cytoprotective chemoresistance factor HSP27. CONCLUSIONS: Despite the deregulation of microtubule organisation, cabazitaxel has been shown to suppress the expression of HSP. Very notably, and may be as a result of down-regulated HSP, cabazitaxel additionally inhibits the expression of the AR in AR-positive PC cells. Thus, cabazitaxel bears an additional anti-proliferative activity which is at least in part specific for PC cells.
PURPOSE:Cabazitaxel, a semi-synthetic taxane of the third generation, inhibits prostate cancer (PC) cell growth by affecting the microtubule architecture. Since cabazitaxel has also been demonstrated to inhibit androgen receptor (AR) functionality, AR and AR-associated heat shock protein (HSP) expressions in the presence of cabazitaxel were characterized. METHODS:AR and HSP expressions were assessed via Western blotting utilizing a PC-cell-line in vitro system incubated with cabazitaxel. RESULTS: Incubation experiments with 0.3 nM cabazitaxel exhibited significantly reduced levels of AR and the AR-associated factors HSP90α, HSP40, and HSP70/HSP90 organising protein. Furthermore, expression of the anti-apoptotic factor HSP60 was suppressed. In contrast to other anticancer compounds, cabazitaxel did not alter the cytoprotective chemoresistance factor HSP27. CONCLUSIONS: Despite the deregulation of microtubule organisation, cabazitaxel has been shown to suppress the expression of HSP. Very notably, and may be as a result of down-regulated HSP, cabazitaxel additionally inhibits the expression of the AR in AR-positive PC cells. Thus, cabazitaxel bears an additional anti-proliferative activity which is at least in part specific for PC cells.
Entities:
Keywords:
Androgen receptor; Cabazitaxel; Chemoresistance; Heat shock proteins; Prostate cancer
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