ArticleCell death & disease2013
Sensitization of melanoma cells for TRAIL-induced apoptosis by BMS-345541 correlates with altered phosphorylation and activation of Bax.
Article in Cell death & disease, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 33 citations in OpenAlex.
- Article
- Enhanced CTLA-4 blockade anti-tumor immunity with APG-157 combination in a murine head and neck cancer.Cancer medicine · 2024Article
- Effective Targeting of Melanoma Cells by Combination of Mcl-1 and Bcl-2/Bcl-xInternational journal of molecular sciences · 2024Article
- Enhancing the Effect of Tumor Necrosis Factor-Related Apoptosis-Inducing Ligand Signaling and Arginine Deprivation in Melanoma.International journal of molecular sciences · 2021Review
- Resistance of melanoma cells to anticancer treatment: a role of vascular endothelial growth factor.Postepy dermatologii i alergologii · 2020Review
- Self-Renewal Signalling Pathway Inhibitors: Perspectives on Therapeutic Approaches for Cancer Stem Cells.OncoTargets and therapy · 2020Review
- Countering TRAIL Resistance in Melanoma.Cancers · 2019Review
- Inhibition of NF-κB Signaling Reduces the Stemness Characteristics of Lung Cancer Stem Cells.Frontiers in oncology · 2018Article
- Unlocking the NF-κB Conundrum: Embracing Complexity to Achieve Specificity.Biomedicines · 2017Review
- Design, synthesis, and biological evaluation of novelDrug design, development and therapy · 2017Article
- IκB kinase b Mediating the Downregulation of p53 and p21 by Lipopolysaccharide in Human Papillomavirus 16Chinese medical journal · 2016Article
- Targeting cell death signalling in cancer: minimising 'Collateral damage'.British journal of cancer · 2016Review
- The alkyllysophospholipid edelfosine enhances TRAIL-mediated apoptosis in gastric cancer cells through death receptor 5 and the mitochondrial pathway.Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine · 2016Article
- Direct Activation of Bax Protein for Cancer Therapy.Medicinal research reviews · 2016Review
- Sensitization of Melanoma Cells for Death Ligand TRAIL Is Based on Cell Cycle Arrest, ROS Production, and Activation of Proapoptotic Bcl-2 Proteins.The Journal of investigative dermatology · 2015Article
- Effects of nuclear factor-κB and ERK signaling transduction pathway inhibitors on human melanoma cell proliferationOncology letters · 2015Article
- Urocortin-2 suppression of p38-MAPK signaling as an additional mechanism for ischemic cardioprotection.Molecular and cellular biochemistry · 2015Article
- Towards combinatorial targeted therapy in melanoma: from pre-clinical evidence to clinical application (review).International journal of oncology · 2014Review
- Indomethacin sensitizes TRAIL-resistant melanoma cells to TRAIL-induced apoptosis through ROS-mediated upregulation of death receptor 5 and downregulation of survivin.The Journal of investigative dermatology · 2014Article
- ROS-dependent phosphorylation of Bax by wortmannin sensitizes melanoma cells for TRAIL-induced apoptosis.Cell death & disease · 2013Article
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Resistance to TRAIL (TNF-related apoptosis-inducing ligand)- induced apoptosis limits its therapeutic use. Different strategies of TRAIL sensitization and a dependency on Bax have been reported, but common principles of TRAIL resistance and the way of Bax activation remained poorly understood. Applying a melanoma model of TRAIL-sensitive and -resistant cell lines, efficient sensitization for TRAIL-induced apoptosis is demonstrated by the kinase inhibitor BMS-345541 (N-(1,8-dimethylimidazo(1,2-a)quinoxalin-4-yl)-1,2-ethanediamine hydrochloride), which targets IκB (inhibitor of κB proteins) kinase β (IKKβ). This effect was completely abrogated by Bax knockout as well as by Bcl-2 overexpression, in accordance with a Bax dependency. Early loss of the mitochondrial membrane potential, release of cytochrome c and Smac (second mitochondria-derived activator of caspases) clearly indicated the activation of mitochondrial apoptosis pathways. Of note, BMS-345541 alone resulted in an early Bax activation, seen by conformational changes and by Bax translocation. The synergistic effects can be explained by Bid activation through TRAIL, which inhibits Bcl-2, and the activation of Bax through BMS-345541. The critical roles of XIAP (X-chromosome-linked inhibitor of apoptosis protein), Smac and Bid were clearly proven by overexpression and siRNA knockdown, respectively. The way of Bax activation by BMS-345541 was unraveled by establishing new assays for Bax activation. These showed reduction of the inactivating Bax phosphorylation at serine-184, while the activating Bax phosphorylation at threonine-167 was enhanced. Thus, modulation of Bax phosphorylation appeared as tightly related to TRAIL sensitivity/resistance in melanoma cells, and therapeutic strategies may be considered.
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