ArticleCancer biology & therapy2014
Regulation of dimethyl-fumarate toxicity by proteasome inhibitors.
Article in Cancer biology & therapy, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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The trial behind it
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
21 citing papers in PubMed, 30 citations in OpenAlex.
- Dimethyl fumarate abrogates hepatocellular carcinoma growth by inhibiting Nrf2/Bcl-xL axis and enhances sorafenib's efficacy.Scientific reports · 2025Article
- Navigating Glioma Complexity: The Role of Abnormal Signaling Pathways in Shaping Future Therapies.Biomedicines · 2025Review
- Repurposing dimethyl fumarate for cancer therapy: current evidence and future directions.Frontiers in pharmacology · 2025Review
- Roles of Glutathione and AP-1 in the Enhancement of Vitamin D-Induced Differentiation by Activators of the Nrf2 Signaling Pathway in Acute Myeloid Leukemia Cells.International journal of molecular sciences · 2024Article
- Dimethyl Fumarate Reduces Inflammation in Chronic Active Multiple Sclerosis Lesions.Neurology(R) neuroimmunology & neuroinflammation · 2022Observational
- Wnt and PI3K/Akt/mTOR Survival Pathways as Therapeutic Targets in Glioblastoma.International journal of molecular sciences · 2022Review
- Article
- The potential roles of Nrf2/Keap1 signaling in anticancer drug interactions.Current research in pharmacology and drug discovery · 2021Review
- Molecular Effects of FDA-Approved Multiple Sclerosis Drugs on Glial Cells and Neurons of the Central Nervous System.International journal of molecular sciences · 2020Review
- Fingolimod Augments Monomethylfumarate Killing of GBM Cells.Frontiers in oncology · 2020Article
- Article
- Role of dimethyl fumarate in the treatment of glioblastoma multiforme: A review article.Iranian journal of neurology · 2019Review
- Multiple Sclerosis and Cancer: The Ying-Yang Effect of Disease Modifying Therapies.Frontiers in immunology · 2019Review
- High Effectiveness in Actions of Carfilzomib on Delayed-Rectifier KFrontiers in pharmacology · 2019Article
- Therapeutic Targeting of TAZ and YAP by Dimethyl Fumarate in Systemic Sclerosis Fibrosis.The Journal of investigative dermatology · 2018Article
- Monomethyl fumarate inhibits pain behaviors and amygdala activity in a rat arthritis model.Pain · 2017Article
- Second-generation proteasome inhibitor carfilzomib sensitizes neuroblastoma cells to doxorubicin-induced apoptosis.Oncotarget · 2016Article
- Repurposing Tecfidera for cancer.Aging · 2016Article
- Ruxolitinib synergizes with DMF to kill via BIM+BAD-induced mitochondrial dysfunction and via reduced SOD2/TRX expression and ROS.Oncotarget · 2016Article
- Rationally Repurposing Ruxolitinib (Jakafi (®)) as a Solid Tumor Therapeutic.Frontiers in oncology · 2016Article
Corrections and comments
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
Abstract
The present studies examined the biology of the multiple sclerosis drug dimethyl-fumarate (DMF) or its in vivo breakdown product and active metabolite mono-methyl-fumarate (MMF), alone or in combination with proteasome inhibitors, in primary human glioblastoma (GBM) cells. MMF enhanced velcade and carfilzomib toxicity in multiple primary GBM isolates. Similar data were obtained in breast and colon cancer cells. MMF reduced the invasiveness of GBM cells, and enhanced the toxicity of ionizing radiation and temozolomide. MMF killed freshly isolated activated microglia which was associated with reduced IL-6, TGFβ and TNFα production. The combination of MMF and the multiple sclerosis drug Gilenya further reduced both GBM and activated microglia viability and cytokine production. Over-expression of c-FLIP-s or BCL(-)XL protected GBM cells from MMF and velcade toxicity. MMF and velcade increased plasma membrane localization of CD95, and knock down of CD95 or FADD blocked the drug interaction. The drug combination inactivated AKT, ERK1/2 and mTOR. Molecular inhibition of AKT/ERK/mTOR signaling enhanced drug combination toxicity whereas molecular activation of these pathways suppressed killing. MMF and velcade increased the levels of autophagosomes and autolysosomes and knock down of ATG5 or Beclin1 protected cells. Inhibition of the eIF2α/ATF4 arm or the IRE1α/XBP1 arm of the ER stress response enhanced drug combination lethality. This was associated with greater production of reactive oxygen species and quenching of ROS suppressed cell killing.
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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.