ArticleJournal of experimental & clinical cancer research : CR2019
Proteasomal cysteine deubiquitinase inhibitor b-AP15 suppresses migration and induces apoptosis in diffuse large B cell lymphoma.
Article in Journal of experimental & clinical cancer research : CR, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.
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Who cites it
32 citing papers in PubMed, 52 citations in OpenAlex.
- Antibody-DNA nanostructure conjugates integrate doxorubicin and rituximab to enhance therapeutic efficacy for DLBCL.Blood advances · 2025Article
- Proteomic Study of Diffuse Large B-Cell Lymphoma Identifying Proteins Associated with R-CHOP Response.Biomedicines · 2025Article
- A novel ubiquitination-based molecular signature predicts prognosis in diffuse large B-cell lymphoma.Annals of hematology · 2025Article
- The role of ubiquitination in health and disease.MedComm · 2024Review
- Targeting USP14/UCHL5: A Breakthrough Approach to Overcoming Treatment-Resistant FLT3-ITD-Positive AML.International journal of molecular sciences · 2024Article
- Antitumor Effects and the Potential Mechanism of 10-HDA against SU-DHL-2 Cells.Pharmaceuticals (Basel, Switzerland) · 2024Article
- C-MYC-activated lncRNA SNHG20 accelerates the proliferation of diffuse large B cell lymphoma via USP14-mediated deubiquitination of β-catenin.Biology direct · 2024Article
- Targeting proteasomal deubiquitinases USP14 and UCHL5 with b-AP15 reduces 5-fluorouracil resistance in colorectal cancer cells.Acta pharmacologica Sinica · 2023Article
- Deubiquitylating Enzymes in Cancer and Immunity.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2023Review
- Antitumor Effects of Poplar Propolis on DLBCL SU-DHL-2 Cells.Foods (Basel, Switzerland) · 2023Article
- Proliferation and migration of ML1 follicular thyroid cancer cells are inhibited by IU1 targeting USP14: role of proteasome and autophagy flux.Frontiers in cell and developmental biology · 2023Article
- Cyclin-dependent kinase 7/9 inhibitor SNS-032 induces apoptosis in diffuse large B-cell lymphoma cells.Cancer biology & therapy · 2022Article
- Inhibition of proteasomal deubiquitinases USP14 and UCHL5 overcomes tyrosine kinase inhibitor resistance in chronic myeloid leukaemia.Clinical and translational medicine · 2022Article
- Altered pathways and targeted therapy in double hit lymphoma.Journal of hematology & oncology · 2022Review
- Pro-apoptotic and anti-apoptotic regulation mediated by deubiquitinating enzymes.Cellular and molecular life sciences : CMLS · 2022Review
- Pharmacological Modulation of Ubiquitin-Proteasome Pathways in Oncogenic Signaling.International journal of molecular sciences · 2021Review
- Proteomic Landscape of Extracellular Vesicles for Diffuse Large B-Cell Lymphoma Subtyping.International journal of molecular sciences · 2021Article
- Deubiquitinases in hematological malignancies.Biomarker research · 2021Review
- Deubiquitinases: Modulators of Different Types of Regulated Cell Death.International journal of molecular sciences · 2021Review
- Current Methods of Post-Translational Modification Analysis and Their Applications in Blood Cancers.Cancers · 2021Review
Corrections and comments
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Authors and funding
10 authors at 3 institutions in 2 countries.
Funding
Abstract
backgroundThe first line therapy for patients with diffuse large B cell (DLBCL) is R-CHOP. About half of DLBCL patients are either refractory to, or will relapse, after the treatment. Therefore, identifying novel drug targets and effective therapeutic agents is urgently needed for improving DLBCL patient survival. b-AP15, a selective small molecule inhibitor of proteasomal USP14 and UCHL5 deubiquitinases (DUBs), has shown selectivity and efficacy in several other types of cancer cells. This is the first study to report the effect of b-AP15 in DLBCL.
methodsCell lines of two DLBCL subtypes, Germinal Center B Cell/ GCB (SU-DHL-4, OCI-LY-1, OCI-LY-19) and Activated B Cell/ABC (SU-DHL-2), were used in the current study. Cell viability was measured by MTS assay, proliferation by trypan blue exclusion staining assay, cellular apoptosis by Annexin V-FITC/PI staining and mitochondrial outer membrane permeability assays, the activities of 20S proteasome peptidases by cleavage of specific fluorogenic substrates, and cell migration was detected by transwell assay in these GCB- and ABC-DLBCL cell lines. Mouse xenograft models of SU-DHL-4 and SU-DHL-2 cells were used to determine in vivo effects of b-AP15 in DLBCL tumors.
resultsb-AP15 inhibited proteasome DUB activities and activated cell death pathway, as evident by caspase activation and mitochondria apoptosis in GCB- and ABC- DLBCL cell lines. b-AP15 treatment suppressed migration of GCB- and ABC-DLBCL cells via inhibiting Wnt/β-catenin and TGFβ/Smad pathways. Additionally, b-AP15 significantly inhibited the growth of GCB- and ABC DLBCL in xenograft models.
conclusionsThese results indicate that b-AP15 inhibits cell migration and induces apoptosis in GCB- and ABC-DLBCL cells, and suggest that inhibition of 19S proteasomal DUB should be a novel strategy for DLBCL treatment.
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Registered trials
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