ArticleCells2019
The Deubiquitinating Enzyme Inhibitor PR-619 Enhances the Cytotoxicity of Cisplatin via the Suppression of Anti-Apoptotic Bcl-2 Protein: In Vitro and In Vivo Study.
Article in Cells, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 28 citations in OpenAlex.
- Otubain deubiquitinases: Multi-layered regulators of cell fate, development, and stress responses across kingdoms.iScience · 2026Review
- USP5 Suppresses Ferroptosis in Bladder Cancer Through Stabilization of GPX4.Current issues in molecular biology · 2025Article
- Native Mass Spectrometry Reveals Binding Interactions of SARS-CoV-2 PLpro with Inhibitors and Cellular Targets.ACS infectious diseases · 2024Article
- P62 promotes FSH-induced antral follicle formation by directing degradation of ubiquitinated WT1.Cellular and molecular life sciences : CMLS · 2024Article
- Ubiquitin-proteasome pathway-mediated regulation of the Bcl-2 family: effects and therapeutic approaches.Haematologica · 2024Review
- Ubiquitin-Specific Proteases as Potential Therapeutic Targets in Bladder Cancer-In Vitro Evaluation of Degrasyn and PR-619 Activity Using Human and Canine Models.Biomedicines · 2023Article
- Regulation of apoptosis by ubiquitination in liver cancer.American journal of cancer research · 2023Review
- Anti-tumor effects of deubiquitinating enzyme inhibitor PR-619 in human chondrosarcoma through reduced cell proliferation and endoplasmic reticulum stress-related apoptosis.American journal of cancer research · 2023Article
- OTUB2 Promotes Proliferation and Migration of Hepatocellular Carcinoma Cells by PJA1 Deubiquitylation.Cellular and molecular bioengineering · 2022Article
- Pharmacological Modulation of Ubiquitin-Proteasome Pathways in Oncogenic Signaling.International journal of molecular sciences · 2021Review
- PR-619, a General Inhibitor of Deubiquitylating Enzymes, Diminishes Cisplatin Resistance in Urothelial Carcinoma Cells through the Suppression of c-Myc: An In Vitro and In Vivo Study.International journal of molecular sciences · 2021Article
- YM155 Inhibits NleB and SseK Arginine Glycosyltransferase Activity.Pathogens (Basel, Switzerland) · 2021Article
- Inhibition of deubiquitination by PR-619 induces apoptosis and autophagy via ubi-protein aggregation-activated ER stress in oesophageal squamous cell carcinoma.Cell proliferation · 2021Article
- THZ1, a covalent CDK7 inhibitor, enhances gemcitabine-induced cytotoxicity via suppression of Bcl-2 in urothelial carcinoma.American journal of cancer research · 2021Article
- Screening of a Focused Ubiquitin-Proteasome Pathway Inhibitor Library Identifies Small Molecules as Novel Modulators of Botulinum Neurotoxin Type A Toxicity.Frontiers in pharmacology · 2021Article
- Article
- Qingxin Kaiqiao Fang Inhibits AEvidence-based complementary and alternative medicine : eCAM · 2020Article
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Authors and funding
11 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
After chemotherapy for the treatment of metastatic bladder urothelial carcinoma (UC), most patients inevitably encounter drug resistance and resultant treatment failure. Deubiquitinating enzymes (DUBs) remove ubiquitin from target proteins and play a critical role in maintaining protein homeostasis. This study investigated the antitumor effect of PR-619, a DUBs inhibitor, in combination with cisplatin, for bladder UC treatment. Our results showed that PR-619 effectively induced dose- and time-dependent cytotoxicity, apoptosis, and ER-stress related apoptosis in human UC (T24 and BFTC-905) cells. Additionally, co-treatment of PR-619 with cisplatin potentiated cisplatin-induced cytotoxicity in UC cells and was accompanied by the concurrent suppression of Bcl-2. We also proved that Bcl-2 overexpression is related to the chemo-resistant status in patients with metastatic UC by immunohistochemistry (IHC) staining. In a xenograft mice model, we confirmed that PR-619 enhanced the antitumor effect of cisplatin on cisplatin-naïve and cisplatin-resistant UCs. Our results demonstrated that PR-619 effectively enhanced the cisplatin-induced antitumor effect via concurrent suppression of the Bcl-2 level. These findings provide promising insight for developing a therapeutic strategy for UC treatment.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.