ArticleOncotarget2017
Sensitization of neuroblastoma for vincristine-induced apoptosis by Smac mimetic LCL161 is attended by G2 cell cycle arrest but is independent of NFκB, RIP1 and TNF-α.
Article in Oncotarget, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed, 17 citations in OpenAlex.
- Focus on necroptosis: its role in the pathogenesis and therapeutic potential of osteoarthritis.Frontiers in immunology · 2026Review
- Research Progress in the Small Molecule Smac Mimetics in Combination Therapy of Cancer.Current medicinal chemistry · 2025Review
- Overcoming cancer drug resistance: insights into Apoptotic pathway modulation by plant-based nanoparticle and natural products.Frontiers in oncology · 2025Review
- Targeting the inhibitors of apoptosis proteins (IAPs) to combat drug resistance in cancers.Frontiers in pharmacology · 2025Review
- Targeting the apoptosis pathway to treat tumours of the paediatric nervous system.Cell death & disease · 2022Review
- A Review of the Current Impact of Inhibitors of Apoptosis Proteins and Their Repression in Cancer.Cancers · 2022Review
- IAP and HDAC inhibitors interact synergistically in myeloma cells through noncanonical NF-κB- and caspase-8-dependent mechanisms.Blood advances · 2021Article
- Intravenous leiomyomatosis is inclined to a solid entity different from uterine leiomyoma based on RNA-seq analysis with RT-qPCR validation.Cancer medicine · 2020Article
- Destined to Die: Apoptosis and Pediatric Cancers.Cancers · 2019Review
- Dual BRD4 and AURKA Inhibition Is Synergistic against MYCN-Amplified and Nonamplified Neuroblastoma.Neoplasia (New York, N.Y.) · 2018Article
- Mackerel-Derived Fermented Fish Oil Promotes Hair Growth by Anagen-Stimulating Pathways.International journal of molecular sciences · 2018Article
- FK506 Attenuates the MRP1-Mediated Chemoresistant Phenotype in Glioblastoma Stem-Like Cells.International journal of molecular sciences · 2018Article
Corrections and comments
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Authors and funding
6 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
We demonstrated sensitization for chemotherapy by Smac mimetic (SM) LCL161, a potent antagonist of inhibitor of apoptosis proteins (IAP), in neuroblastoma (NB). Vinca alkaloids, particularly vincristine (VCR), displayed the strongest impact on inhibition of proliferation and apoptosis induction in combination with LCL161. The underlying signaling pathways remain elusive, though. LCL161 induces a quick degradation of cellular IAP 1 (cIAP-1). Combination of LCL161 with VCR had only marginal effects on X-linked IAP (XIAP) protein expression. Cell death is accompanied by activation of intrinsic (caspase-9 and MMP) and extrinsic (caspase-8) pathways of apoptosis, repression of migratory potential and cell cycle arrest in G2 phase. LCL161-induced cIAP degradation leads to activation of non-canonical and blockade of canonical NF-κB pathways but not induction of apoptosis. Surprisingly NF-κB and TNF-α signaling is negligible for VCR- and VCR/LCL161-induced apoptosis since chemical inhibition of NF-κB using BAY-7085 and PBS-1086, as well as application of TNF-α blocking antibody Humira (adalimumab) has no relevant effect on cell death. Recently formation of a TNF-α-independent complex (ripoptosome) consisting of RIP1, FADD and caspase-8 following IAP inhibition by SM has been described. However, targeting of RIP1 by Necrostatin was not sufficient to influence apoptosis induced by VCR/LCL161.
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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.