ArticlePloS one2014
Separate and combined effects of DNMT and HDAC inhibitors in treating human multi-drug resistant osteosarcoma HosDXR150 cell line.
Article in PloS one, 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, 47 citations in OpenAlex.
- From Bench to Bedside: Advancements in Precision Oncology and Drug Discovery for Osteosarcoma.Cancers · 2026Review
- Systemic strategies for osteosarcoma: advances and future directions.Discover oncology · 2025Review
- Advancements in Osteosarcoma Therapy: Overcoming Chemotherapy Resistance and Exploring Novel Pharmacological Strategies.Pharmaceuticals (Basel, Switzerland) · 2025Review
- Review
- Augmented Therapeutic Potential of EC-Synthetic Retinoids in Caco-2 Cancer Cells Using an In Vitro Approach.International journal of molecular sciences · 2022Article
- Osteosarcoma mechanobiology and therapeutic targets.British journal of pharmacology · 2022Review
- Expression and methylation status ofGastroenterology and hepatology from bed to bench · 2022Article
- Article
- Epigenetic DNA Methylation ofInternational journal of molecular sciences · 2021Article
- The Histone Deacetylase Inhibitor Entinostat/Syndax 275 in Osteosarcoma.Advances in experimental medicine and biology · 2020Review
- Reversal of increased mammary tumorigenesis by valproic acid and hydralazine in offspring of dams fed high fat diet during pregnancy.Scientific reports · 2019Article
- Knockdown of KCNQ1OT1 Suppresses Cell Invasion and Sensitizes Osteosarcoma Cells to CDDP by Upregulating DNMT1-Mediated Kcnq1 Expression.Molecular therapy. Nucleic acids · 2019Article
- Article
- Activation of Estrogen Receptor Alpha by Decitabine Inhibits Osteosarcoma Growth and Metastasis.Cancer research · 2019Article
- The histone deacetylase inhibitor Suberoylanilide Hydroxamic Acid (SAHA) as a therapeutic agent in rhabdomyosarcoma.Cancer biology & therapy · 2019Article
- Histone deacetylase inhibitor ITF2357 leads to apoptosis and enhances doxorubicin cytotoxicity in preclinical models of human sarcoma.Oncogenesis · 2018Article
- Validation of epigenetic mechanisms regulating gene expression in canine B-cell lymphoma: An in vitro and in vivo approach.PloS one · 2018Article
- Histone deacetylation, as opposed to promoter methylation, results in epigeneticOncology letters · 2018Article
- Therapeutic applications of histone deacetylase inhibitors in sarcoma.Cancer treatment reviews · 2017Review
- Combination of azacitidine and trichostatin A decreased the tumorigenic potential of lung cancer cells.OncoTargets and therapy · 2017Article
Corrections and comments
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Authors and funding
8 authors at 2 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Understanding the molecular mechanisms underlying multi-drug resistance (MDR) is one of the major challenges in current cancer research. A phenomenon which is common to both intrinsic and acquired resistance, is the aberrant alteration of gene expression in drug-resistant cancers. Although such dysregulation depends on many possible causes, an epigenetic characterization is considered a main driver. Recent studies have suggested a direct role for epigenetic inactivation of genes in determining tumor chemo-sensitivity. We investigated the effects of the inhibition of DNA methyltransferase (DNMT) and hystone deacethylase (HDAC), considered to reverse the epigenetic aberrations and lead to the re-expression of de novo methylated genes in MDR osteosarcoma (OS) cells. Based on our analysis of the HosDXR150 cell line, we found that in order to reduce cell proliferation, co-treatment of MDR OS cells with DNMT (5-Aza-dC, DAC) and HDAC (Trichostatin A, TSA) inhibitors is more effective than relying on each treatment alone. In re-expressing epigenetically silenced genes induced by treatments, a very specific regulation takes place which suggests that methylation and de-acetylation have occurred either separately or simultaneously to determine MDR OS phenotype. In particular, functional relationships have been reported after measuring differential gene expression, indicating that MDR OS cells acquired growth and survival advantage by simultaneous epigenetic inactivation of both multiple p53-independent apoptotic signals and osteoblast differentiation pathways. Furthermore, co-treatment results more efficient in inducing the re-expression of some main pathways according to the computed enrichment, thus emphasizing its potential towards representing an effective therapeutic option for MDR OS.
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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.