Cabazitaxel Inhibits Prostate Cancer Cell Growth by Inhibition of Androgen Receptor and Heat Shock Protein Expression

Overview

Journal World J Urol

Specialty Urology

Date 2019 Jan 4

PMID 30603780

Citations 7

Authors

Anja-Martina Rottach

Hannes Ahrend

Benedikt Martin

Reinhard Walther

Uwe Zimmermann

Martin Burchardt

Matthias B Stope

Affiliations

Soon will be listed here.

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.

Citing Articles

The exported J domain proteins fine-tune human and malarial Hsp70s: pathological exploitation of proteostasis machinery.

Almaazmi S, Kaur R, Singh H, Blatch G Front Mol Biosci. 2023; 10:1216192.

PMID: 37457831 PMC: 10349383. DOI: 10.3389/fmolb.2023.1216192.

Impact of Non-Invasive Physical Plasma on Heat Shock Protein Functionality in Eukaryotic Cells.

Wang Y, Abazid A, Badendieck S, Mustea A, Stope M Biomedicines. 2023; 11(5).

PMID: 37239142 PMC: 10216214. DOI: 10.3390/biomedicines11051471.

Synthetic Small Molecule Modulators of Hsp70 and Hsp40 Chaperones as Promising Anticancer Agents.

Nitzsche B, Hopfner M, Biersack B Int J Mol Sci. 2023; 24(4).

PMID: 36835501 PMC: 9964478. DOI: 10.3390/ijms24044083.

Physiological and Genetically Engineered Expression Modulation Methods Do Not Affect Cellular Levels of the Heat Shock Protein HSP60 in Prostate Cancer Cells.

Erb H, Streitborger A, Mustea A, Stope M In Vivo. 2022; 36(2):596-602.

PMID: 35241511 PMC: 8931909. DOI: 10.21873/invivo.12742.

Cabazitaxel suppresses colorectal cancer cell growth via enhancing the p53 antitumor pathway.

Zhang W, Sun R, Zhang Y, Hu R, Li Q, Wu W FEBS Open Bio. 2021; 11(11):3032-3050.

PMID: 34496154 PMC: 8564099. DOI: 10.1002/2211-5463.13290.

References

Parker C, Nilsson S, Heinrich D, Helle S, OSullivan J, Fossa S . Alpha emitter radium-223 and survival in metastatic prostate cancer. N Engl J Med. 2013; 369(3):213-23. DOI: 10.1056/NEJMoa1213755. View

Scott E . Chemohormonal therapy in metastatic hormone-sensitive prostate cancer. Sweeney CJ, Chen YH, Carducci M, Liu G, Jarrard DF, Eisenberger M, Wong YN, Hahn N, Kohli M, Cooney MM, Dreicer R, Vogelzang NJ, Picus J, Shevrin D, Hussain M, Garcia JA, DiPaola.... Urol Oncol. 2017; 35(3):123. DOI: 10.1016/j.urolonc.2016.12.021. View

Seidenfeld J, Samson D, Hasselblad V, Aronson N, Albertsen P, Bennett C . Single-therapy androgen suppression in men with advanced prostate cancer: a systematic review and meta-analysis. Ann Intern Med. 2000; 132(7):566-77. DOI: 10.7326/0003-4819-132-7-200004040-00009. View

Vrignaud P, Semiond D, Lejeune P, Bouchard H, Calvet L, Combeau C . Preclinical antitumor activity of cabazitaxel, a semisynthetic taxane active in taxane-resistant tumors. Clin Cancer Res. 2013; 19(11):2973-83. DOI: 10.1158/1078-0432.CCR-12-3146. View

Beer T, Ryan C, Venner P, Petrylak D, Chatta G, Ruether J . Intermittent chemotherapy in patients with metastatic androgen-independent prostate cancer: results from ASCENT, a double-blinded, randomized comparison of high-dose calcitriol plus docetaxel with placebo plus docetaxel. Cancer. 2007; 112(2):326-30. DOI: 10.1002/cncr.23163. View

Petrylak D, Tangen C, Hussain M, Lara Jr P, Jones J, Taplin M . Docetaxel and estramustine compared with mitoxantrone and prednisone for advanced refractory prostate cancer. N Engl J Med. 2004; 351(15):1513-20. DOI: 10.1056/NEJMoa041318. View

Stope M, Schubert T, Staar D, Ronnau C, Streitborger A, Kroeger N . Effect of the heat shock protein HSP27 on androgen receptor expression and function in prostate cancer cells. World J Urol. 2012; 30(3):327-31. DOI: 10.1007/s00345-012-0843-z. View

Gibbons N, Watson R, Coffey R, Brady H, Fitzpatrick J . Heat-shock proteins inhibit induction of prostate cancer cell apoptosis. Prostate. 2000; 45(1):58-65. DOI: 10.1002/1097-0045(20000915)45:1<58::aid-pros7>3.0.co;2-#. View

Cookson M, Roth B, Dahm P, Engstrom C, Freedland S, Hussain M . Castration-resistant prostate cancer: AUA Guideline. J Urol. 2013; 190(2):429-38. DOI: 10.1016/j.juro.2013.05.005. View

10.

Grossebrummel H, Peter T, Mandelkow R, Weiss M, Muzzio D, Zimmermann U . Cytochrome P450 17A1 inhibitor abiraterone attenuates cellular growth of prostate cancer cells independently from androgen receptor signaling by modulation of oncogenic and apoptotic pathways. Int J Oncol. 2015; 48(2):793-800. DOI: 10.3892/ijo.2015.3274. View

11.

Mezynski J, Pezaro C, Bianchini D, Zivi A, Sandhu S, Thompson E . Antitumour activity of docetaxel following treatment with the CYP17A1 inhibitor abiraterone: clinical evidence for cross-resistance?. Ann Oncol. 2012; 23(11):2943-2947. DOI: 10.1093/annonc/mds119. View

12.

Zhu M, Horbinski C, Garzotto M, Qian D, Beer T, Kyprianou N . Tubulin-targeting chemotherapy impairs androgen receptor activity in prostate cancer. Cancer Res. 2010; 70(20):7992-8002. PMC: 2978028. DOI: 10.1158/0008-5472.CAN-10-0585. View

13.

Small E, Schellhammer P, Higano C, Redfern C, Nemunaitis J, Valone F . Placebo-controlled phase III trial of immunologic therapy with sipuleucel-T (APC8015) in patients with metastatic, asymptomatic hormone refractory prostate cancer. J Clin Oncol. 2006; 24(19):3089-94. DOI: 10.1200/JCO.2005.04.5252. View

14.

Tang D, Khaleque M, Jones E, Theriault J, Li C, Wong W . Expression of heat shock proteins and heat shock protein messenger ribonucleic acid in human prostate carcinoma in vitro and in tumors in vivo. Cell Stress Chaperones. 2005; 10(1):46-58. PMC: 1074571. DOI: 10.1379/csc-44r.1. View

15.

Stope M, Weiss M, Preuss M, Streitborger A, Ritter C, Zimmermann U . Immediate and transient phosphorylation of the heat shock protein 27 initiates chemoresistance in prostate cancer cells. Oncol Rep. 2014; 32(6):2380-6. DOI: 10.3892/or.2014.3492. View

16.

Cappello F, Rappa F, David S, Anzalone R, Zummo G . Immunohistochemical evaluation of PCNA, p53, HSP60, HSP10 and MUC-2 presence and expression in prostate carcinogenesis. Anticancer Res. 2003; 23(2B):1325-31. View

17.

CORNFORD P, Dodson A, Parsons K, Desmond A, Woolfenden A, Fordham M . Heat shock protein expression independently predicts clinical outcome in prostate cancer. Cancer Res. 2001; 60(24):7099-105. View

18.

So A, Hadaschik B, Sowery R, Gleave M . The role of stress proteins in prostate cancer. Curr Genomics. 2008; 8(4):252-61. PMC: 2430682. DOI: 10.2174/138920207781386951. View

19.

Katzenwadel A, Wolf P . Androgen deprivation of prostate cancer: Leading to a therapeutic dead end. Cancer Lett. 2015; 367(1):12-7. DOI: 10.1016/j.canlet.2015.06.021. View

20.

. Immediate versus deferred treatment for advanced prostatic cancer: initial results of the Medical Research Council Trial. The Medical Research Council Prostate Cancer Working Party Investigators Group. Br J Urol. 1997; 79(2):235-46. DOI: 10.1046/j.1464-410x.1997.d01-6840.x. View