Mortezavi, Ashkan; Salemi, Souzan; Kranzbühler, Benedikt; Gross, Oliver; Sulser, Tullio; Simon, Hans-Uwe; Eberli, Daniel (2019). Inhibition of autophagy significantly increases the antitumor effect of Abiraterone in prostate cancer. World journal of urology, 37(2), pp. 351-358. Springer-Verlag 10.1007/s00345-018-2385-5
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PURPOSE
Abiraterone acetate (AA) plus prednisone is an approved treatment of advanced prostate cancer (PCa). Autophagy is linked to drug resistance in numerous types of cancers. We hypothesized, that upregulation of autophagy is one of the mechanisms by which PCa cells survive AA anti-tumor treatment and therefore evaluated the potential effect of a combination with autophagy inhibition.
METHODS
Human PCa LNCaP cell lines were cultured in steroid-free medium and treated with AA. Autophagy was inhibited by 3-methyladenine, chloroquine and ATG5 siRNA knock-down. Cell viability and apoptosis was assessed by flow cytometry and fluorescence microscopy, and autophagy was monitored by immunohistochemistry, AUTOdot and Western blotting.
RESULTS
Western blot revealed upregulation of ATG5 and LC3 II with a reduction of p62 protein expression in AA-treated cells, indicating upregulation of autophagy. These data were supported by results obtained with immunocytochemistry and AUTOdot assays. Using flow cytometry, we showed that combining AA with autophagy inhibition significantly impaired cell viability (1.3-1.6-fold, p < 0.001) and increased apoptosis (1.4-1.5-fold, p < 0.001) compared to AA treatment alone.
CONCLUSIONS
AA activates autophagy as a cytoprotective mechanism in LNCaP prostate cancer cells and targeting of autophagy enhances the antitumor effect of the compound.
Item Type: |
Journal Article (Original Article) |
|---|---|
Division/Institute: |
04 Faculty of Medicine > Pre-clinic Human Medicine > Institute of Pharmacology |
UniBE Contributor: |
Simon, Hans-Uwe |
Subjects: |
600 Technology > 610 Medicine & health |
ISSN: |
0724-4983 |
Publisher: |
Springer-Verlag |
Language: |
English |
Submitter: |
Jana Berger |
Date Deposited: |
10 Jul 2018 09:09 |
Last Modified: |
05 Dec 2022 15:16 |
Publisher DOI: |
10.1007/s00345-018-2385-5 |
PubMed ID: |
29951789 |
Uncontrolled Keywords: |
Abiraterone Autophagy PCa |
BORIS DOI: |
10.7892/boris.118416 |
URI: |
https://boris.unibe.ch/id/eprint/118416 |
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