ArticleCurrent cancer drug targets2013
The histone deacetylase inhibitor, MS-275 (entinostat), downregulates c-FLIP, sensitizes osteosarcoma cells to FasL, and induces the regression of osteosarcoma lung metastases.
Article in Current cancer drug targets, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 41 citations in OpenAlex.
- ADAR2 induces the differentiation of osteosarcoma cells by editing activity on IGFBP7: new implications for therapy.Bone research · 2026Article
- Modeling Therapeutic Targets: β-Globin Disorders and Beyond.Advances in experimental medicine and biology · 2026Review
- Osteosarcoma mechanobiology and therapeutic targets.British journal of pharmacology · 2022Review
- HDAC inhibitor, MS-275, increases vascular permeability by suppressing Robo4 expression in endothelial cells.Tissue barriers · 2021Article
- A phase 1 study of entinostat in children and adolescents with recurrent or refractory solid tumors, including CNS tumors: Trial ADVL1513, Pediatric Early Phase-Clinical Trial Network (PEP-CTN).Pediatric blood & cancer · 2021Article
- Prospects for NK Cell Therapy of Sarcoma.Cancers · 2020Review
- The Histone Deacetylase Inhibitor Entinostat/Syndax 275 in Osteosarcoma.Advances in experimental medicine and biology · 2020Review
- Understanding and Modeling Metastasis Biology to Improve Therapeutic Strategies for Combating Osteosarcoma Progression.Frontiers in oncology · 2020Review
- Review
- Protein profiling of osteosarcoma tissue and soft callus unveils activation of the unfolded protein response pathway.International journal of oncology · 2019Article
- Synthesis and antiproliferative assay of triazolyl-2,2-dimethyl-3-phenylpropanoates as potential HDAC inhibitors.RSC advances · 2019Article
- Expression patterns of class I histone deacetylases in osteosarcoma: a novel prognostic marker with potential therapeutic implications.Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc · 2018Article
- Droxinostat sensitizes human colon cancer cells to apoptotic cell death via induction of oxidative stress.Cellular & molecular biology letters · 2018Article
- Therapeutic applications of histone deacetylase inhibitors in sarcoma.Cancer treatment reviews · 2017Review
- Article
- The histone deacetylase inhibiting drug Entinostat induces lipid accumulation in differentiated HepaRG cells.Scientific reports · 2016Article
- Histone Deacetylases in Bone Development and Skeletal Disorders.Physiological reviews · 2015Review
- The narrow-spectrum HDAC inhibitor entinostat enhances NKG2D expression without NK cell toxicity, leading to enhanced recognition of cancer cells.Pharmaceutical research · 2015Article
- Molecular profiling of childhood cancer: Biomarkers and novel therapies.BBA clinical · 2014Review
- Advances in therapy for pediatric sarcomas.Current oncology reports · 2014Review
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
The purpose of this study was to determine the effects of the histone deacetylase inhibitor, MS-275, on the Fas signaling pathway and susceptibility of osteosarcoma (OS) to Fas ligand (FasL)-induced cell death. OS metastasizes almost exclusively to the lungs. We have shown that Fas expression in OS cells is inversely correlated with their metastatic potential. Fas(+) cells are rapidly eliminated when they enter the lungs via interaction with FasL, which is constitutively expressed in the lungs. Fas(-) OS cells escape this FasL-induced apoptosis and survive in the lung microenvironment. Moreover, upregulation of Fas in established OS lung metastases results in tumor regression. Therefore, agents that upregulate Fas expression or activate the Fas signaling pathway may have therapeutic potential. Treatment of Fas(-) metastatic OS cell lines with 2 µM MS-275 sensitized cells to FasL-induced cell death in vitro. We found that MS-275 did not alter the expression of Fas on the cell surface; rather it resulted in the downregulation of the anti-apoptotic protein, c-FLIP (cellular FLICE-inhibitory protein), by inhibiting c-FLIP mRNA. Downregulation of c- FLIP correlated with caspase activation and apoptosis induction. Treatment of nu/nu-mice with established OS lung metastases with oral MS-275 resulted in tumor regression, increased apoptosis and a significant inhibition of c-FLIP expression in tumors. Histopathological examination of mice showed no evidence of significant toxicity. Overall, these results suggest that the mechanism by which MS-275 sensitizes OS cells and lung metastases to FasL-induced cell death may be by a direct reduction in the expression of c-FLIP.
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Registered trials
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