Modulation of the Prostate Cancer Resistance Factor Hsp27 by the Chemotherapeutic Drugs Abiraterone, Cabazitaxel, Docetaxel and Enzalutamide

Research output: Contribution to journalResearch articleContributedpeer-review

Contributors

  • Jennifer H S Küster - , University of Bonn Medical Center (Author)
  • Holger H H Erb - , Department of Urology (Author)
  • Hannes Ahrend - , Israelite Hospital in Hamburg (Author)
  • Alexander Abazid - , German Federal Armed Forces Hospital Berlin (Author)
  • Matthias B Stope - , University of Bonn Medical Center (Author)

Abstract

BACKGROUND/AIM: The cytoprotective heat shock protein 27 (HSP27) acts as a protein chaperone, antioxidant, and apoptosis regulator and is involved in cytoskeletal remodeling in prostate cancer. This study was designed to assess the effect of prostate cancer therapeutics on HSP27 to identify drugs that may benefit from an HSP27 inhibitor combination therapy.

MATERIALS AND METHODS: Cell counting was utilized to assess drug treatment efficiency. Changes in protein levels after drug treatment were assessed using western blot analysis.

RESULTS: Abiraterone, cabazitaxel, docetaxel and enzalutamide significantly reduced cell proliferation in LNCaP and PC3 cells. Treatment with abiraterone and enzalutamide led to a significant reduction in HSP27 protein levels. In contrast, treatment with cabazitaxel and docetaxel did not change the HSP27 protein levels.

CONCLUSION: Treatment with abiraterone and enzalutamide reduces HSP27 protein in an AR-independent manner and thus suppresses HSP27-correlated resistance mechanisms. However, docetaxel and cabazitaxel do not alter HSP27 protein levels, so that taxanes' efficacy may be enhanced by combining them with HSP27-inhibiting drugs.

Details

Original languageEnglish
Pages (from-to)2815-2821
Number of pages7
JournalAnticancer research
Volume44
Issue number7
Publication statusPublished - Jul 2024
Peer-reviewedYes

External IDs

Scopus 85197133261

Keywords

Sustainable Development Goals

Keywords

  • Humans, Male, Taxoids/pharmacology, Docetaxel/pharmacology, Phenylthiohydantoin/pharmacology, Benzamides, Nitriles, HSP27 Heat-Shock Proteins/metabolism, Drug Resistance, Neoplasm/drug effects, Prostatic Neoplasms/drug therapy, Androstenes/pharmacology, Antineoplastic Agents/pharmacology, Cell Line, Tumor, Cell Proliferation/drug effects, Molecular Chaperones/metabolism, Heat-Shock Proteins/metabolism