The heat shock protein 70 inhibitor VER155008 suppresses the expression of HSP27, HOP and HSP90β and the androgen receptor, induces apoptosis, and attenuates prostate cancer cell growth
| Autor: | Martin Burchardt, Clara Langer, Luise Zimmermann, Daniela Brünnert, Manik Chatterjee, Ralf C. Bargou, Matthias B. Stope |
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| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
Male HSP27 Heat-Shock Proteins Antineoplastic Agents Apoptosis urologic and male genital diseases Biochemistry 03 medical and health sciences Prostate cancer Inhibitory Concentration 50 0302 clinical medicine Hsp27 Heat shock protein Cell Line Tumor LNCaP medicine Humans HSP90 Heat-Shock Proteins Annexin A5 Molecular Biology Heat-Shock Proteins Cell Proliferation biology Chemistry Cell Cycle Prostatic Neoplasms Cell Biology Purine Nucleosides Prostate-Specific Antigen medicine.disease Hsp70 Androgen receptor 030104 developmental biology Receptors Androgen 030220 oncology & carcinogenesis Caspases Cancer research biology.protein HSP60 G1 phase |
| Zdroj: | Journal of cellular biochemistry. 121(1) |
| ISSN: | 1097-4644 |
| Popis: | Heat shock proteins (HSPs) are molecular chaperones that play a pivotal role in correct folding, stabilization and intracellular transport of many client proteins including those involved in oncogenesis. HSP70, which is frequently overexpressed in prostate cancer (PCa), has been shown to critically contribute to tumor cell survival, and might therefore represent a potential therapeutic target. We treated both the androgen receptor (AR)-positive LNCaP and the AR-negative PC-3 cell lines with the pharmacologic HSP70 inhibitor VER155008. Although we observed antiproliferative effects and induction of apoptosis upon HSP70 inhibition, the apoptotic effect was more pronounced in AR-positive LNCaP cells. In addition, VER155008 treatment induced G1 cell cycle arrest in LNCaP cells and decreased AR expression. Further analysis of the HSP system by Western blot analysis revealed that expression of HSP27, HOP and HSP90β was significantly inhibited by VER155008 treatment, whereas the HSP40, HSP60, and HSP90α expression remained unchanged. Taken together, VER155008 might serve as a novel therapeutic option in PCa patients independent of the AR expression status. |
| Databáze: | OpenAIRE |
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