ArticleInternational journal of oncology2016
Overcoming resistance to TRAIL-induced apoptosis in solid tumor cells by simultaneously targeting death receptors, c-FLIP and IAPs.
Article in International journal of oncology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 43 papers.
What it found
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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
43 citing papers in PubMed, 91 citations in OpenAlex.
- Mesenchymal Stem Cells Expressing CES1 and Soluble TRAIL Activate CPT-11 and Induce Apoptosis in Lung Cancer Brain Metastatic Lesions.Cancer research communications · 2025Article
- Ionizing Radiation Increases Death Receptor 5 (DR5)-Mediated Cell Death, but Not Death Receptor 4 (DR4)-Mediated Cell Death in 3D Tumor Spheroids.International journal of molecular sciences · 2025Article
- Low extracellular pH enhances TRAIL-induced apoptosis by downregulating Mcl-1 expression.Experimental cell research · 2025Article
- Comprehensive landscape of cell death mechanisms: from molecular cross-talk to therapeutic innovation in oncology.Frontiers in cell and developmental biology · 2025Review
- Review
- NK cell line modified to express a potent, DR5 specific variant of TRAIL, show enhanced cytotoxicity in ovarian cancer models.Heliyon · 2024Article
- Review
- Cellular signaling crosstalk between Wnt signaling and gap junctions inbenzo[a]pyrene toxicity.Cell biology and toxicology · 2023Article
- An Antidepressant Drug Increased TRAIL Receptor-2 Expression and Sensitized Lung Cancer Cells to TRAIL-induced Apoptosis.Anti-cancer agents in medicinal chemistry · 2023Article
- RNA-seq and Single-Cell Transcriptome Analyses of TRAIL Receptors Gene Expression in Human Osteosarcoma Cells and Tissues.Cancer informatics · 2023Article
- Indirubin Inhibits TRAIL-Induced Activation of Death Receptor 5 in Jurkat Cells.Natural product communications · 2023Article
- Exosomal delivery of TRAIL and miR‑335 for the treatment of hepatocellular carcinoma (Review).International journal of molecular medicine · 2023Review
- Review
- Tumour Derived Extracellular Vesicles: Challenging Target to Blunt Tumour Immune Evasion.Cancers · 2022Review
- Kaempferol sensitizes tumor necrosis factor-related apoptosis-inducing ligand-resistance chronic myelogenous leukemia cells to apoptosis.Molecular biology reports · 2022Article
- Article
- Cytotoxic Engineered Induced Neural Stem Cells as an Intravenous Therapy for Primary Non-Small Cell Lung Cancer and Triple-Negative Breast Cancer.Molecular cancer therapeutics · 2021Article
- Effects of Curcumin Analogues DMC and EF24 in Combination with the Cytokine TRAIL against Kidney Cancer.Molecules (Basel, Switzerland) · 2021Article
- Small-Molecule Natural Product Physachenolide C Potentiates Immunotherapy Efficacy by Targeting BET Proteins.Cancer research · 2021Article
- Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
9 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The discovery of the TRAIL protein and its death receptors DR4/5 changed the horizon of cancer research because TRAIL specifically kills cancer cells. However, the validity of TRAIL-based cancer therapies has yet to be established, as most cancer cells are TRAIL-resistant. In this report, we demonstrate that TRAIL-resistance of many cancer cell lines can be overcome after siRNA- or rocaglamide-mediated downregulation of c-FLIP expression and simultaneous inhibition of IAPs activity using AT406, a pan-antagonist of IAPs. Combined triple actions of the TRAIL, the IAPs inhibitor, AT406, and the c-FLIP expression inhibitor, rocaglamide (ART), markedly improve TRAIL-induced apoptotic effects in most solid cancer cell lines through the activation of an extrinsic apoptosis pathway. Furthermore, this ART combination does not harm normal cells. Among the 18 TRAIL-resistant cancer cell lines used, 15 cell lines become sensitive or highly sensitive to ART, and two out of three glioma cell lines exhibit high resistance to ART treatment due to very low levels of procaspase-8. This study provides a rationale for the development of TRAIL-induced apoptosis-based cancer therapies.
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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.