Combined Treatments with a Retinoid Receptor Agonist and Epigenetic Modulators in Human Neuroblastoma Cells
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Updated: Mar 12, 2026
Analysis of Retinoic Acid-induced Neural Differentiation of Mouse Embryonic Stem Cells in Two and Three-dimensional Embryoid Bodies
Published on: April 22, 2017
Viviane Rösner Almeida1,2, Igor Araujo Vieira3, Marienela Buendia1,2
1Cancer and Neurobiology Laboratory, Experimental Research Center, Clinical Hospital (CPE-HCPA), Federal University of Rio Grande do Sul, Porto Alegre, RS, 90035-003, Brazil.
Abstract:
Neuroblastoma (NB) is the most common extracranial solid childhood tumor accounting for around 15% of pediatric cancer deaths and most probably originates from a failure in the development of embryonic neural crest cells. Retinoids can inhibit the proliferation and stimulate differentiation of NB cells. In addition, epigenetic events involving changes in chromatin structure and DNA methylation can mediate the effects of retinoids; hence, the scope of this study is to investigate the use of retinoids and epigenetic drugs in NB cell lines. Here, we demonstrate that the combination of retinoid all trans-retinoic acid (ATRA) with inhibitors of either histone deacetylases (HDACs) or DNA methyltransferase is more effective in impairing the proliferation of human SH-SY5Y and SK-N-BE(2) NB cells than any drug given alone. Treatments also induced differential changes on the messenger RNA (mRNA) expression of retinoid receptor subtypes and reduced the protein content of c-Myc, the neuronal markers NeuN and β-3 tubulin, and the oncoprotein Bmi1. These results suggest that the combination of retinoids with epigenetic modulators is more effective in reducing NB growth than treatment with single drugs.
Insights
Combining retinoids with epigenetic drugs like HDAC or DNA methyltransferase inhibitors significantly reduces neuroblastoma (NB) cell proliferation. This combination therapy is more effective than single-drug treatments for childhood cancer.
Area of Science:
- Pediatric Oncology
- Cancer Biology
- Epigenetics
Background:
- Neuroblastoma (NB) is a common pediatric cancer originating from neural crest cells.
- Retinoids show potential in inhibiting NB cell proliferation and promoting differentiation.
- Epigenetic modifications, including DNA methylation and chromatin structure, influence retinoid effects.
Purpose of the Study:
- To investigate the combined efficacy of retinoids and epigenetic drugs in neuroblastoma cell lines.
- To evaluate the impact of combined treatments on NB cell proliferation and differentiation markers.
Main Methods:
- Utilized human neuroblastoma cell lines (SH-SY5Y and SK-N-BE(2)).
- Administered all-trans-retinoic acid (ATRA) in combination with histone deacetylase (HDAC) or DNA methyltransferase (DNMT) inhibitors.
- Assessed cell proliferation, messenger RNA (mRNA) expression of retinoid receptor subtypes, and protein levels of c-Myc, NeuN, β-3 tubulin, and Bmi1.
Main Results:
- Combined ATRA with HDAC or DNMT inhibitors was more effective in inhibiting NB cell proliferation than single agents.
- Treatments led to altered mRNA expression of retinoid receptor subtypes.
- Reduced protein levels of c-Myc, neuronal markers (NeuN, β-3 tubulin), and oncoprotein Bmi1 were observed.
Conclusions:
- Combination therapy of retinoids and epigenetic modulators offers a more potent strategy for reducing neuroblastoma growth.
- This approach warrants further investigation for potential therapeutic applications in pediatric neuroblastoma.
