ArticleBMC cancer2009
A Smac-mimetic sensitizes prostate cancer cells to TRAIL-induced apoptosis via modulating both IAPs and NF-kappaB.
Article in BMC cancer, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers.
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Who cites it
40 citing papers in PubMed, 70 citations in OpenAlex.
- Nano-TRAIL: a promising path to cancer therapy.Cancer drug resistance (Alhambra, Calif.) · 2023Review
- BH3-mimetics: recent developments in cancer therapy.Journal of experimental & clinical cancer research : CR · 2021Review
- Behind the Adaptive and Resistance Mechanisms of Cancer Stem Cells to TRAIL.Pharmaceutics · 2021Review
- Smac mimetics and TRAIL cooperate to induce MLKL-dependent necroptosis in Burkitt's lymphoma cell lines.Neoplasia (New York, N.Y.) · 2021Article
- Smac mimetics LCL161 and GDC-0152 inhibit osteosarcoma growth and metastasis in mice.BMC cancer · 2019Article
- Understanding Apoptosis and Apoptotic Pathways Targeted Cancer Therapeutics.Advanced pharmaceutical bulletin · 2019Review
- Oncolytic viro-chemotherapy exhibits antitumor effect in laryngeal squamous cell carcinoma cells and mouse xenografts.Cancer management and research · 2019Article
- IAP Antagonists Enhance Cytokine Production from Mouse and Human iNKT Cells.Cancer immunology research · 2018Article
- Aconitine inhibits the proliferation of hepatocellular carcinoma by inducing apoptosis.International journal of clinical and experimental pathology · 2018Article
- Overcoming chemotherapy drug resistance by targeting inhibitors of apoptosis proteins (IAPs).Apoptosis : an international journal on programmed cell death · 2017Review
- Article
- Potential of apoptotic pathway-targeted cancer therapeutic research: Where do we stand?Cell death & disease · 2016Review
- Carbon-ion beams effectively induce growth inhibition and apoptosis in human neural stem cells compared with glioblastoma A172 cells.Journal of radiation research · 2015Article
- High levels of X-linked Inhibitor-of-Apoptosis Protein (XIAP) are indicative of radio chemotherapy resistance in rectal cancer.Radiation oncology (London, England) · 2015Article
- Overcoming tumor immune evasion with an unique arbovirus.Journal of translational medicine · 2015Review
- Mechanism of Arctigenin-Induced Specific Cytotoxicity against Human Hepatocellular Carcinoma Cell Lines: Hep G2 and SMMC7721.PloS one · 2015Article
- Rotundarpene prevents TRAIL-induced apoptosis in human keratinocytes by suppressing the caspase-8- and Bid-pathways and the mitochondrial pathway.Naunyn-Schmiedeberg's archives of pharmacology · 2014Article
- Differential response of head and neck cancer cell lines to TRAIL or Smac mimetics is associated with the cellular levels and activity of caspase-8 and caspase-10.British journal of cancer · 2014Article
- Bortezomib sensitizes non-small cell lung cancer to mesenchymal stromal cell-delivered inducible caspase-9-mediated cytotoxicity.Cancer gene therapy · 2014Article
- Menadione induces the formation of reactive oxygen species and depletion of GSH-mediated apoptosis and inhibits the FAK-mediated cell invasion.Naunyn-Schmiedeberg's archives of pharmacology · 2014Article
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
backgroundAlthough tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is a promising agent for human cancer therapy, prostate cancer still remains resistant to TRAIL. Both X-linked inhibitor of apoptosis (XIAP) and nuclear factor-kappaB function as key negative regulators of TRAIL signaling. In this study, we evaluated the effect of SH122, a small molecule mimetic of the second mitochondria-derived activator of caspases (Smac), on TRAIL-induced apoptosis in prostate cancer cells.
methodsThe potential of Smac-mimetics to bind XIAP or cIAP-1 was examined by pull-down assay. Cytotoxicity of TRAIL and/or Smac-mimetics was determined by a standard cell growth assay. Silencing of XIAP or cIAP-1 was achieved by transient transfection of short hairpin RNA. Apoptosis was detected by Annexin V-PI staining followed by flow cytometry and by Western Blot analysis of caspases, PARP and Bid. NF-kappaB activation was determined by subcellular fractionation, real time RT-PCR and reporter assay.
resultsSH122, but not its inactive analog, binds to XIAP and cIAP-1. SH122 significantly sensitized prostate cancer cells to TRAIL-mediated cell death. Moreover, SH122 enhanced TRAIL-induced apoptosis via both the death receptor and the mitochondrial pathway. Knockdown of both XIAP and cIAP-1 sensitized cellular response to TRAIL. XIAP-knockdown attenuated sensitivity of SH122 to TRAIL-induced cytotoxicity, confirming that XIAP is an important target for IAP-inhibitor-mediated TRAIL sensitization. SH122 also suppressed TRAIL-induced NF-kappaB activation by preventing cytosolic IkappaB-alpha degradation and RelA nuclear translocation, as well as by suppressing NF-kappaB target gene expression.
conclusionThese results demonstrate that SH122 sensitizes human prostate cancer cells to TRAIL-induced apoptosis by mimicking Smac and blocking both IAPs and NF-kappaB. Modulating IAPs may represent a promising approach to overcoming TRAIL-resistance in human prostate cancer with constitutively active NF-kappaB signaling.
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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.