ArticleThe Journal of biological chemistry2011
Modulation of CCAAT/enhancer binding protein homologous protein (CHOP)-dependent DR5 expression by nelfinavir sensitizes glioblastoma multiforme cells to tumor necrosis factor-related apoptosis-inducing ligand (TRAIL).
Article in The Journal of biological chemistry, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.
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Who cites it
34 citing papers in PubMed, 61 citations in OpenAlex.
- Efficacy of nelfinavir as monotherapy in refractory adenoid cystic carcinoma: Results of a phase II clinical trial.Head & neck · 2015Trial
- Neurotoxicity of the antineoplastic drugs: "Doxorubicin" as an example.Journal of molecular histology · 2024Review
- Repurposing approved non-oncology drugs for cancer therapy: a comprehensive review of mechanisms, efficacy, and clinical prospects.European journal of medical research · 2023Review
- Endoplasmic Reticulum Stress in the Brain Tumor Immune Microenvironment.Molecular cancer research : MCR · 2023Article
- Target receptor identification and subsequent treatment of resected brain tumors with encapsulated and engineered allogeneic stem cells.Nature communications · 2022Article
- Drug Repurposing for Glioblastoma and Current Advances in Drug Delivery-A Comprehensive Review of the Literature.Biomolecules · 2021Review
- Overcoming TRAIL Resistance for Glioblastoma Treatment.Biomolecules · 2021Review
- Dihydroartemisinin-Transferrin Adducts Enhance TRAIL-Induced Apoptosis in Triple-Negative Breast Cancer in a P53-Independent and ROS-Dependent Manner.Frontiers in oncology · 2021Article
- Review
- Stress Management: Death Receptor Signalling and Cross-Talks with the Unfolded Protein Response in Cancer.Cancers · 2020Review
- Characterizing Cell Stress and GRP78 in Glioma to Enhance Tumor Treatment.Frontiers in oncology · 2020Review
- Anticancer Function and ROS-Mediated Multi-Targeting Anticancer Mechanisms of Copper (II) 2-hydroxy-1-naphthaldehyde Complexes.Molecules (Basel, Switzerland) · 2019Article
- Article
- An Integrated Stress Response Agent that Modulates DR5-Dependent TRAIL Synergy Reduces Patient-Derived Glioma Stem Cell Viability.Molecular cancer research : MCR · 2019Article
- Ciprofloxacin Enhances TRAIL-Induced Apoptosis in Lung Cancer Cells by Upregulating the Expression and Protein Stability of Death Receptors through CHOP Expression.International journal of molecular sciences · 2018Article
- Activating Transcription Factor 3 as a Novel Regulator of Chemotherapy Response in Breast Cancer.Translational oncology · 2018Article
- Isochaihulactone-induced DDIT3 causes ER stress-PERK independent apoptosis in glioblastoma multiforme cells.Oncotarget · 2017Article
- Thapsigargin sensitizes human esophageal cancer to TRAIL-induced apoptosis via AMPK activation.Scientific reports · 2016Article
- Ginsenoside compound K sensitizes human colon cancer cells to TRAIL-induced apoptosis via autophagy-dependent and -independent DR5 upregulation.Cell death & disease · 2016Article
- Inhibition of Notch1 signaling overcomes resistance to the death ligand Trail by specificity protein 1-dependent upregulation of death receptor 5.Cell death & disease · 2015Article
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
Human glioblastoma multiforme cells demonstrate varying levels of sensitivity to tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)-induced apoptosis. Endoplasmic reticulum (ER) stress has been shown to trigger cell death through apoptosis. We therefore pursued a strategy of integrating clinically relevant investigational agents that cooperate mechanistically through the regulation of ER stress and apoptosis pathways. Nelfinavir belongs to the protease inhibitor class of drugs currently used to treat patients with HIV and is in clinical trials as an anti-tumor agent. We found that Nelfinavir treatment led to ER stress-induced up-regulation of the DR5 receptor. This transactivation was mediated by the transcription factor CCAAT/enhancer binding protein homologous protein (CHOP). We also determined that ER stress-induced ATF4 up-regulation was responsible for modulation of CHOP. In contrast, DR4 receptor expression was unchanged by Nelfinavir treatment. Combining Nelfinavir with TRAIL led to a significantly enhanced level of apoptosis that was abrogated by siRNA silencing of DR5. We provide evidence that Nelfinavir-induced ER stress modulates DR5 expression in human glioblastoma multiforme cells and can enhance TRAIL efficacy. These studies provide a potential mechanistic rationale for the use of the Food and Drug Administration-approved agent Nelfinavir in combination with DR5 agonists to induce apoptosis in human malignancies.
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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.