ArticleThe Journal of biological chemistry2013
Azadirone, a limonoid tetranortriterpene, induces death receptors and sensitizes human cancer cells to tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) through a p53 protein-independent mechanism: evidence for the role of the ROS-ERK-CHOP-death receptor pathway.
Article in The Journal of biological chemistry, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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Who cites it
25 citing papers in PubMed, 60 citations in OpenAlex.
- Advances in the study of death receptor 5.Frontiers in pharmacology · 2025Review
- Nimbolide: promising agent for prevention and treatment of chronic diseases (recent update).Food & nutrition research · 2024Article
- Exploring the therapeutic potential of Neem (Annals of translational medicine · 2022Review
- Induction of DR5-Dependent Apoptosis by PGAMolecules (Basel, Switzerland) · 2022Article
- Leveling Up the Controversial Role of Neutrophils in Cancer: When the Complexity Becomes Entangled.Cells · 2021Review
- Traditional Chinese medicines and their active ingredients sensitize cancer cells to TRAIL-induced apoptosis.Journal of Zhejiang University. Science. B · 2021Review
- Harnessing TRAIL-Induced Apoptosis Pathway for Cancer Immunotherapy and Associated Challenges.Frontiers in immunology · 2021Review
- Alternol Sensitizes Renal Carcinoma Cells to TRAIL-Induced Apoptosis.Frontiers in pharmacology · 2021Article
- Article
- Epicatechin Prevents Methamphetamine-Induced Neuronal Cell Death via Inhibition of ER Stress.Biomolecules & therapeutics · 2019Article
- Developing TRAIL/TRAIL death receptor-based cancer therapies.Cancer metastasis reviews · 2018Review
- Z-FL-COCHO, a cathepsin S inhibitor, enhances oxaliplatin-mediated apoptosis through the induction of endoplasmic reticulum stress.Experimental & molecular medicine · 2018Article
- Limonoids from seeds ofActa pharmaceutica Sinica. B · 2018Article
- Tetrandrine (TET) Induces Death Receptors Apo Trail R1 (DR4) and Apo Trail R2 (DR5) and Sensitizes Prostate Cancer Cells to TRAIL-Induced Apoptosis.Molecular cancer therapeutics · 2018Article
- Melatonin as a potential inhibitory agent in head and neck cancer.Oncotarget · 2017Review
- Transcription Factor C/EBP Homologous Protein in Health and Diseases.Frontiers in immunology · 2017Review
- Valosin-containing Protein is a Target of 5'-l Fuligocandin B and Enhances TRAIL Resistance in Cancer Cells.ChemistryOpen · 2016Article
- A new brominated chalcone derivative suppresses the growth of gastric cancer cells in vitro and in vivo involving ROS mediated up-regulation of DR5 and 4 expression and apoptosis.Toxicology and applied pharmacology · 2016Article
- Regulation of breast tumorigenesis through acid sensors.Oncogene · 2016Article
- Comprehensive identification of genes driven by ERV9-LTRs reveals TNFRSF10B as a re-activatable mediator of testicular cancer cell death.Cell death and differentiation · 2016Article
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Authors and funding
5 authors at 3 institutions in 2 countries.
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Abstract
Although tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) has shown efficacy in a phase 2 clinical trial, development of resistance to TRAIL by tumor cells is a major roadblock. We investigated whether azadirone, a limonoidal tetranortriterpene, can sensitize human tumor cells to TRAIL. Results indicate that azadirone sensitized cancer cells to TRAIL. The limonoid induced expression of death receptor (DR) 5 and DR4 but did not affect expression of decoy receptors in cancer cells. The induction of DRs was mediated through activation of ERK and through up-regulation of a transcription factor CCAAT enhancer-binding protein homologous protein (CHOP) as silencing of these signaling molecules abrogated the effect of azadirone. These effects of azadirone were cancer cell-specific. The CHOP binding site on the DR5 gene was required for induction of DR5 by azadirone. Up-regulation of DRs was mediated through the generation of reactive oxygen species (ROS) as ROS scavengers reduced the effect of azadirone on ERK activation, CHOP up-regulation, DR induction, and TRAIL sensitization. The induction of DRs by this limonoid was independent of p53, but sensitization to TRAIL was p53-dependent. The limonoid down-regulated the expression of cell survival proteins and up-regulated the proapoptotic proteins. The combination of azadirone with TRAIL was found to be additive at concentrations lower than IC50, whereas at higher concentrations, the combination was synergistic. Overall, this study indicates that azadirone can sensitize cancer cells to TRAIL through ROS-ERK-CHOP-mediated up-regulation of DR5 and DR4 signaling, down-regulation of cell survival proteins, and up-regulation of proapoptotic proteins.
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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.