ArticleTumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine2014
Smac mimetic compound LCL161 sensitizes esophageal carcinoma cells to radiotherapy by inhibiting the expression of inhibitor of apoptosis protein.
Article in Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
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Who cites it
27 citing papers in PubMed, 42 citations in OpenAlex.
- IAP antagonists induce anti-tumor immunity in multiple myeloma.Nature medicine · 2016Trial
- IAPs in cancers: molecular mechanisms, clinical prognostic value, and translational therapeutic potential.Journal of translational medicine · 2026Review
- The critical role of X-linked inhibitor of apoptosis protein (XIAP) in tumor development.Apoptosis : an international journal on programmed cell death · 2025Review
- Research Progress in the Small Molecule Smac Mimetics in Combination Therapy of Cancer.Current medicinal chemistry · 2025Review
- Characterization of a Potent and Orally Bioavailable Lys-Covalent Inhibitor of Apoptosis Protein (IAP) Antagonist.Journal of medicinal chemistry · 2023Article
- FoxM1 knockdown enhanced radiosensitivity of esophageal cancer by inducing apoptosis.Journal of Cancer · 2023Article
- Ginsenoside Rg3 enhances the radiosensitivity of lung cancer A549 and H1299 cells via the PI3K/AKT signaling pathway.In vitro cellular & developmental biology. Animal · 2023Article
- Unraveling the Complexity of Regulated Cell Death in Esophageal Cancer: from Underlying Mechanisms to Targeted Therapeutics.International journal of biological sciences · 2023Review
- Targeting Apoptosis in Cancer.Current oncology reports · 2022Review
- Stability and Cell Permeability of Sulfonyl Fluorides in the Design of Lys-Covalent Antagonists of Protein-Protein Interactions.ChemMedChem · 2020Article
- Structure-based design, synthesis, and evaluation of the biological activity of novel phosphoroorganic small molecule IAP antagonists.Investigational new drugs · 2020Article
- Review
- Future Therapeutic Directions for Smac-Mimetics.Cells · 2020Review
- Aryl-fluorosulfate-based Lysine Covalent Pan-Inhibitors of Apoptosis Protein (IAP) Antagonists with Cellular Efficacy.Journal of medicinal chemistry · 2019Article
- PAR-4 overcomes chemo-resistance in breast cancer cells by antagonizing cIAP1.Scientific reports · 2019Article
- LCL161, a SMAC-mimetic, Preferentially Radiosensitizes Human Papillomavirus-negative Head and Neck Squamous Cell Carcinoma.Molecular cancer therapeutics · 2019Article
- The SMAC mimetic LCL-161 displays antitumor activity in preclinical models of rituximab-resistant B-cell lymphoma.Blood advances · 2018Article
- Evolution of In Silico Strategies for Protein-Protein Interaction Drug Discovery.Molecules (Basel, Switzerland) · 2018Review
- Endoplasmic reticulum stress-induced degradation of DNAJB12 stimulates BOK accumulation and primes cancer cells for apoptosis.The Journal of biological chemistry · 2017Article
- Overcoming chemotherapy drug resistance by targeting inhibitors of apoptosis proteins (IAPs).Apoptosis : an international journal on programmed cell death · 2017Review
Corrections and comments
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Authors and funding
16 authors at 7 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Currently, unresectable esophageal squamous cell carcinoma (ESCC) is primarily treated by chemoradiotherapy. However, the outcome has not improved significantly due to radioresistance of cancer cells. This study aimed to determine the radiosensitizing effect of LCL161, a novel second mitochondrial-derived activator of caspase (Smac) mimetic, in ESCC cells. ESCC cell lines were treated with LCL161 or radiation, alone or in combination. Cell proliferation was detected by MTT assay. Radiosensitization was evaluated by clonogenic survival assay. Cell apoptosis was detected by flow cytometry. The results showed that LCL161 potently sensitized ESCC cells to radiation with a sensitization enhancement ratio of 1.4-2.0. LCL161 increased radiation-induced DNA double-stranded breaks and promoted the apoptosis of ESCC cells, which could be abrogated by a pan-caspase inhibitor z-VAD-FMK. Furthermore, LCL161 decreased the level of cIAP1 in ESCC cells in a dose-dependent manner and synthesized with irradiation to promote the activation of caspase 8 and the upregulation of TNFα expression in ESCC cells. In conclusion, LCL161 acts as a strong radiosensitizer in human esophageal cancer cells by inhibiting the expression of cIAP1 and promoting the activation of caspase 8, leading to enhanced apoptosis.
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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.