ArticleBlood2009
Caspase-8 dependent histone acetylation by a novel proteasome inhibitor, NPI-0052: a mechanism for synergy in leukemia cells.
Article in Blood, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
31 citing papers in PubMed, 65 citations in OpenAlex.
- Trial
- The novel orally active proteasome inhibitor K-7174 exerts anti-myeloma activity in vitro and in vivo by down-regulating the expression of class I histone deacetylases.The Journal of biological chemistry · 2013Trial
- Higher sperm H3K4me3 levels are associated with idiopathic recurrent pregnancy loss.Epigenetics · 2025Article
- N6-methyladenosine RNA methylation regulator-related alternative splicing gene signature as prognostic predictor and in immune microenvironment characterization of patients with low-grade glioma.Frontiers in genetics · 2022Article
- Enriching cancer pharmacology with drugs of marine origin.British journal of pharmacology · 2020Review
- HDAC Inhibitors in Acute Myeloid Leukemia.Cancers · 2019Review
- (Immuno)proteasomes as therapeutic target in acute leukemia.Cancer metastasis reviews · 2017Review
- Therapeutic Strategies against Epstein-Barr Virus-Associated Cancers Using Proteasome Inhibitors.Viruses · 2017Review
- Induction of cell death by the novel proteasome inhibitor marizomib in glioblastoma in vitro and in vivo.Scientific reports · 2016Article
- Efficacy of panobinostat and marizomib in acute myeloid leukemia and bortezomib-resistant models.Leukemia research · 2015Article
- Antileukemic activity and mechanism of drug resistance to the marine Salinispora tropica proteasome inhibitor salinosporamide A (Marizomib).Molecular pharmacology · 2014Article
- Efficacious proteasome/HDAC inhibitor combination therapy for primary effusion lymphoma.The Journal of clinical investigation · 2013Article
- Phase 1 clinical trial of the novel proteasome inhibitor marizomib with the histone deacetylase inhibitor vorinostat in patients with melanoma, pancreatic and lung cancer based on in vitro assessments of the combination.Investigational new drugs · 2012Article
- The 26S proteasome complex: an attractive target for cancer therapy.Biochimica et biophysica acta · 2012Review
- Specific and prolonged proteasome inhibition dictates apoptosis induction by marizomib and its analogs.Chemico-biological interactions · 2011Article
- Carfilzomib interacts synergistically with histone deacetylase inhibitors in mantle cell lymphoma cells in vitro and in vivo.Molecular cancer therapeutics · 2011Article
- Inhibition of LSD1 sensitizes glioblastoma cells to histone deacetylase inhibitors.Neuro-oncology · 2011Article
- GSI-I (Z-LLNle-CHO) inhibits γ-secretase and the proteosome to trigger cell death in precursor-B acute lymphoblastic leukemia.Leukemia · 2011Article
- Proteasome inhibitors in cancer therapy.Journal of cell communication and signaling · 2011Article
- Marizomib, a proteasome inhibitor for all seasons: preclinical profile and a framework for clinical trials.Current cancer drug targets · 2011Review
Corrections and comments
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
Combination studies of histone deacetylase inhibitors (HDACi) and proteasome inhibitors are providing preclinical framework to build better strategies against hematologic malignancies. Our previous work found that a novel proteasome inhibitor, NPI-0052, and HDACi synergistically induce apoptosis in leukemia cells in a caspase-8- and oxidant-dependent manner. Here we extend those observations to primary leukemia cells and identify novel mechanisms of synergy. Because the proximal targets of NPI-0052 and HDACi are inhibition of proteasome activity and histone acetylation, we initially examined those biochemical events. Increased acetylation of histone-H3 was detected in Jurkat and CLL primary cells treated with NPI-0052, alone or in combination with various HDACi (MS/SNDX-275 or vorinostat). Hyperacetylation by NPI-0052 occurred to a lesser extent in caspase-8-deficient cells and in cells treated with an antioxidant. These results indicate that NPI-0052 is eliciting caspase-8 and oxidative stress-dependent epigenetic alterations. In addition, real-time PCR revealed that MS/SNDX-275 repressed expression of the proteasomal beta5, beta2, and beta1 subunits, consequently inhibiting respective enzymatic activities. Overall, our results suggest that crosstalk by NPI-0052 and HDACi are contributing, along with caspase-8 activation and oxidative stress, to their synergistic cytotoxic effects in leukemia cells, reinforcing the potential clinical utility of combining these 2 agents.
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Registered trials
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.