ArticleThe Journal of investigative dermatology2014
Indomethacin sensitizes TRAIL-resistant melanoma cells to TRAIL-induced apoptosis through ROS-mediated upregulation of death receptor 5 and downregulation of survivin.
Article in The Journal of investigative dermatology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.
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31 citing papers in PubMed, 55 citations in OpenAlex.
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- Stigmasterol Exerts an Anti-Melanoma Property through Down-Regulation of Reactive Oxygen Species and Programmed Cell Death Ligand 1 in Melanoma Cells.Antioxidants (Basel, Switzerland) · 2024Article
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- Anti-Melanoma Activity of Indomethacin Incorporated into Mesoporous Silica Nanoparticles.Pharmaceutical research · 2020Article
- PDE5 and PDE10 inhibition activates cGMP/PKG signaling to block Wnt/β-catenin transcription, cancer cell growth, and tumor immunity.Drug discovery today · 2020Review
- Endoplasmic Reticulum Stress Contributes to Indomethacin-Induced Glioma Apoptosis.International journal of molecular sciences · 2020Article
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- Indomethacin Disrupts Autophagic Flux by Inducing Lysosomal Dysfunction in Gastric Cancer Cells and Increases Their Sensitivity to Cytotoxic Drugs.Scientific reports · 2018Article
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- Matrine-Type Alkaloids Inhibit Advanced Glycation End Products Induced Reactive Oxygen Species-Mediated Apoptosis of Aortic Endothelial Cells In Vivo and In Vitro by Targeting MKK3 and p38MAPK Signaling.Journal of the American Heart Association · 2017Article
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7 authors at 1 institution in 1 country.
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No grant is acknowledged in the PubMed record.
Abstract
Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) has attracted considerable attention owing to its selective killing of tumor cells but not normal cells. Melanoma shows weak response to TRAIL because of its low level of TRAIL death receptors. Here, we investigated whether indomethacin, a nonsteroidal anti-inflammatory drug, can potentiate TRAIL-induced apoptosis in melanoma cells. We showed that indomethacin was capable of promoting TRAIL-induced cell death and apoptosis in A375 melanoma cells. Mechanistically, indomethacin induced cell surface expression of death receptor 5 (DR5) in melanoma cells and also in various types of cancer cells. DR5 knockdown abolished the enhancing effect of indomethacin on TRAIL responses. Induction of the DR5 by indomethacin was found to be p53 independent but dependent on the induction of CCAAT/enhancer-binding protein homologous protein (CHOP). Knockdown of CHOP abolished indomethacin-induced DR5 expression and the associated potentiation of TRAIL-mediated cell death. In addition, indomethacin-induced reactive oxygen species (ROS) production preceded upregulation of CHOP and DR5, and consequent sensitization of cells to TRAIL. We also found that indomethacin treatment downregulated survivin via ROS and the NF-κB-mediated signaling pathways. Interestingly, indomethacin also converted TRAIL-resistant melanoma MeWo and SK-MEL-5 cells into TRAIL-sensitive cells. Taken together, our results indicate that indomethacin can potentiate TRAIL-induced apoptosis through upregulation of death receptors and downregulation of survivin.
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