ArticleCancer immunology, immunotherapy : CII2018
The novel deubiquitinase inhibitor b-AP15 induces direct and NK cell-mediated antitumor effects in human mantle cell lymphoma.
Article in Cancer immunology, immunotherapy : CII, 2018. 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.
- Effect of deubiquitinases in head and neck squamous cell carcinoma (Review).Oncology letters · 2025Review
- Loss of the proteasomal deubiquitinase USP14 induces growth defects and a senescence phenotype in colorectal cancer cells.Scientific reports · 2024Article
- The UCHL5 inhibitor b-AP15 overcomes cisplatin resistance via suppression of cancer stemness in urothelial carcinoma.Molecular therapy oncolytics · 2022Article
- Inhibition of proteasomal deubiquitinases USP14 and UCHL5 overcomes tyrosine kinase inhibitor resistance in chronic myeloid leukaemia.Clinical and translational medicine · 2022Article
- Comprehensive Target Screening and Cellular Profiling of the Cancer-Active Compound b-AP15 Indicate Abrogation of Protein Homeostasis and Organelle Dysfunction as the Primary Mechanism of Action.Frontiers in oncology · 2022Article
- Deubiquitinases in hematological malignancies.Biomarker research · 2021Review
- VLX1570 induces apoptosis through the generation of ROS and induction of ER stress on leukemia cell lines.Cancer science · 2021Article
- Promising Anti-Mitochondrial Agents for Overcoming Acquired Drug Resistance in Multiple Myeloma.Cells · 2021Review
- Advances in Deubiquitinating Enzyme Inhibition and Applications in Cancer Therapeutics.Cancers · 2020Review
- DUBs Activating the Hedgehog Signaling Pathway: A Promising Therapeutic Target in Cancer.Cancers · 2020Review
- Drug Development Targeting the Ubiquitin-Proteasome System (UPS) for the Treatment of Human Cancers.Cancers · 2020Review
- Deubiquitinase Inhibitor b-AP15 Attenuated LPS-Induced Inflammation via Inhibiting ERK1/2, JNK, and NF-Kappa B.Frontiers in molecular biosciences · 2020Article
- Regulatory interplay between deubiquitinating enzymes and cytokines.Cytokine & growth factor reviews · 2019Review
- The Deubiquitinase Inhibitor b-AP15 and Its Effect on Phenotype and Function of Monocyte-Derived Dendritic Cells.Neoplasia (New York, N.Y.) · 2019Article
- Analysis of determinants for in vitro resistance to the small molecule deubiquitinase inhibitor b-AP15.PloS one · 2019Article
- Oxidative Stress Induced by the Deubiquitinase Inhibitor b-AP15 Is Associated with Mitochondrial Impairment.Oxidative medicine and cellular longevity · 2019Article
- Expression of the Immune Checkpoint Modulator OX40 in Acute Lymphoblastic Leukemia Is Associated with BCR-ABL Positivity.Neoplasia (New York, N.Y.) · 2018Article
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Authors and funding
13 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The first therapeutic proteasome inhibitor bortezomib has clinical efficacy in mantle cell lymphoma (MCL) which resulted in its incorporation in treatment algorithms for this disease. Impairment of proteasomal function by bortezomib is mediated via inhibition of the 20S core particle. However, proteasome function can also be modified by targeting upstream components of the ubiquitin-proteasome system. Recently, b-AP15 has been identified as a small molecule achieving proteasome inhibition by targeting the deubiquitinase (DUB) activity of the 19S regulatory subunit and was found to inhibit cancer cell growth in preclinical analyses. In the present study, both direct antitumor effects and the possibility to induce natural killer group 2 member D ligands (NKG2DL) to reinforce NK cell immunity with b-AP15 were investigated to provide a rational basis for clinical evaluation of this novel DUB inhibitor in MCL. Treatment with b-AP15 resulted in reduced viability as well as induction of apoptosis in a time- and dose-dependent manner, which could be attributed to caspase activation in MCL cells. In addition, treatment with b-AP15 differentially induced NKG2DL expression and subsequent NK cell lysis of MCL cells. These results indicate that the DUB inhibitor b-AP15 displays substantial antitumor activity in human MCL and suggest that b-AP15 might be a novel therapeutic option in the treatment of MCL that warrants clinical investigation.
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