ArticleMolecular carcinogenesis2013
Bortezomib-induced sensitization of malignant human glioma cells to vorinostat-induced apoptosis depends on reactive oxygen species production, mitochondrial dysfunction, Noxa upregulation, Mcl-1 cleavage, and DNA damage.
Article in Molecular carcinogenesis, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 43 papers.
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Who cites it
43 citing papers in PubMed, 60 citations in OpenAlex.
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- Targeting mitochondrial energetics reverses panobinostat- and marizomib-induced resistance in pediatric and adult high-grade gliomas.Molecular oncology · 2023Article
- Repurposing FDA-approved drugs as inhibitors of therapy-induced invadopodia activity in glioblastoma cells.Molecular and cellular biochemistry · 2023Article
- In situ Electrochemical Evaluation of the Interaction of dsDNA with the Proteasome Inhibitor Anticancer Drug Bortezomib.Molecules (Basel, Switzerland) · 2023Article
- Proteasome inhibition targets the KMT2A transcriptional complex in acute lymphoblastic leukemia.Nature communications · 2023Article
- Introducing HDAC-Targeting Radiopharmaceuticals for Glioblastoma Imaging and Therapy.Pharmaceuticals (Basel, Switzerland) · 2023Review
- Development of an MCL-1-related prognostic signature and inhibitors screening for glioblastoma.Frontiers in pharmacology · 2023Article
- Integrative Analysis of a Novel Eleven-Small Nucleolar RNA Prognostic Signature in Patients With Lower Grade Glioma.Frontiers in oncology · 2021Article
- Targeting NADMolecular cancer research : MCR · 2020Article
- Silencing lncRNA LOC101928963 Inhibits Proliferation and Promotes Apoptosis in Spinal Cord Glioma Cells by Binding to PMAIP1.Molecular therapy. Nucleic acids · 2019Article
- Therapeutic strategies for diffuse midline glioma from high-throughput combination drug screening.Science translational medicine · 2019Article
- Inhibition of BET Proteins and Histone Deacetylase (HDACs): Crossing Roads in Cancer Therapy.Cancers · 2019Review
- Counteracting survival functions of EBNA3C in Epstein-Barr virus (EBV)-driven lymphoproliferative diseases by combination of SAHA and bortezomib.Oncotarget · 2018Article
- Mitochondrial dysfunction RAD51, and Ku80 proteolysis promote apoptotic effects of Dinaciclib in Bcl-xL silenced cells.Molecular carcinogenesis · 2018Article
- HDAC inhibitor PAC-320 induces G2/M cell cycle arrest and apoptosis in human prostate cancer.Oncotarget · 2018Article
- Therapeutic Potential of Thymoquinone in Glioblastoma Treatment: Targeting Major Gliomagenesis Signaling Pathways.BioMed research international · 2018Review
- Mcl-1 regulates reactive oxygen species via NOX4 during chemotherapy-induced senescence.Oncotarget · 2017Article
- Survivin inhibitor YM155 induces mitochondrial dysfunction, autophagy, DNA damage and apoptosis in Bcl-xL silenced glioma cell lines.Molecular carcinogenesis · 2017Article
- Therapeutic potential and functional interaction of carfilzomib and vorinostat in T-cell leukemia/lymphoma.Oncotarget · 2016Article
- Nuclear factor-κB in glioblastoma: insights into regulators and targeted therapy.Neuro-oncology · 2016Review
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
Glioblastomas are invasive tumors with poor prognosis despite current therapies. Histone deacetylase inhibitors (HDACIs) represent a class of agents that can modulate gene expression to reduce tumor growth, and we and others have noted some antiglioma activity from HDACIs, such as vorinostat, although insufficient to warrant use as monotherapy. We have recently demonstrated that proteasome inhibitors, such as bortezomib, dramatically sensitized highly resistant glioma cells to apoptosis induction, suggesting that proteasomal inhibition may be a promising combination strategy for glioma therapeutics. In this study, we examined whether bortezomib could enhance response to HDAC inhibition in glioma cells. Although primary cells from glioblastoma multiforme (GBM) patients and established glioma cell lines did not show significant induction of apoptosis with vorinostat treatment alone, the combination of vorinostat plus bortezomib significantly enhanced apoptosis. The enhanced efficacy was due to proapoptotic mitochondrial injury and increased generation of reactive oxygen species. Our results also revealed that combination of bortezomib with vorinostat enhanced apoptosis by increasing Mcl-1 cleavage, Noxa upregulation, Bak and Bax activation, and cytochrome c release. Further downregulation of Mcl-1 using shRNA enhanced cell killing by the bortezomib/vorinostat combination. Vorinostat induced a rapid and sustained phosphorylation of histone H2AX in primary GBM and T98G cells, and this effect was significantly enhanced by co-administration of bortezomib. Vorinostat/bortezomib combination also induced Rad51 downregulation, which plays an important role in the synergistic enhancement of DNA damage and apoptosis. The significantly enhanced antitumor activity that results from the combination of bortezomib and HDACIs offers promise as a novel treatment for glioma patients.
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