ArticleNeoplasia (New York, N.Y.)2011
Requirement of nuclear factor κB for Smac mimetic-mediated sensitization of pancreatic carcinoma cells for gemcitabine-induced apoptosis.
Article in Neoplasia (New York, N.Y.), 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 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
17 citing papers in PubMed, 35 citations in OpenAlex.
- Dual-targeting peptides@PMO, a mimetic to the pro-apoptotic protein Smac/DIABLO for selective activation of apoptosis in cancer cells.Frontiers in pharmacology · 2023Article
- Article
- LCL161, a SMAC-mimetic, Preferentially Radiosensitizes Human Papillomavirus-negative Head and Neck Squamous Cell Carcinoma.Molecular cancer therapeutics · 2019Article
- DEBIO 1143, an IAP inhibitor, reverses carboplatin resistance in ovarian cancer cells and triggers apoptotic or necroptotic cell death.Scientific reports · 2018Article
- Article
- Birinapant (TL32711) Improves Responses to GEM/AZD7762 Combination Therapy in Triple-negative Breast Cancer Cell Lines.Anticancer research · 2016Article
- Differential role of RIP1 in Smac mimetic-mediated chemosensitization of neuroblastoma cells.Oncotarget · 2015Article
- SMAC mimetic Debio 1143 synergizes with taxanes, topoisomerase inhibitors and bromodomain inhibitors to impede growth of lung adenocarcinoma cells.Oncotarget · 2015Article
- Mechanism-based mathematical modeling of combined gemcitabine and birinapant in pancreatic cancer cells.Journal of pharmacokinetics and pharmacodynamics · 2015Article
- Article
- The SMAC mimetic BV6 sensitizes colorectal cancer cells to ionizing radiation by interfering with DNA repair processes and enhancing apoptosis.Radiation oncology (London, England) · 2015Article
- Molecular Mechanisms by Which a Fucus vesiculosus Extract Mediates Cell Cycle Inhibition and Cell Death in Pancreatic Cancer Cells.Marine drugs · 2015Article
- Identification of IRF1 as critical dual regulator of Smac mimetic-induced apoptosis and inflammatory cytokine response.Cell death & disease · 2014Article
- Cancer subclonal genetic architecture as a key to personalized medicine.Neoplasia (New York, N.Y.) · 2013Article
- Identification of DR5 as a critical, NF-κB-regulated mediator of Smac-induced apoptosis.Cell death & disease · 2013Article
- A Smac mimetic augments the response of urothelial cancer cells to gemcitabine and cisplatin.Cancer biology & therapy · 2013Article
- Targeting IAP proteins for therapeutic intervention in cancer.Nature reviews. Drug discovery · 2012Review
Corrections and comments
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Defects in apoptosis contribute to treatment resistance and poor outcome of pancreatic cancer, calling for novel therapeutic strategies. Here, we provide the first evidence that nuclear factor (NF) κB is required for Smac mimetic-mediated sensitization of pancreatic carcinoma cells for gemcitabine-induced apoptosis. The Smac mimetic BV6 cooperates with gemcitabine to reduce cell viability and to induce apoptosis. In addition, BV6 significantly enhances the cytotoxicity of several anticancer drugs against pancreatic carcinoma cells, including doxorubicin, cisplatin, and 5-fluorouracil. Molecular studies reveal that BV6 stimulates NF-κB activation, which is further increased in the presence of gemcitabine. Importantly, inhibition of NF-κB by overexpression of the dominant-negative IκBα superrepressor significantly decreases BV6- and gemcitabine-induced apoptosis, demonstrating that NF-κB exerts a proapoptotic function in this model of apoptosis. In support of this notion, inhibition of tumor necrosis factor α (TNFα) by the TNFα blocking antibody Enbrel reduces BV6- and gemcitabine-induced activation of caspase 8 and 3, loss of mitochondrial membrane potential, and apoptosis. By demonstrating that BV6 and gemcitabine trigger a NF-κB-dependent, TNFα-mediated loop to activate apoptosis signaling pathways and caspase-dependent apoptotic cell death, our findings have important implications for the development of Smac mimetic-based combination protocols in the treatment of pancreatic cancer.
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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.