ArticleMolecular neurobiology2025
Bexarotene Promotes Neuroblastoma SH-SY5Y Cell Differentiation to Mature Neurons with Decreased Proliferation.
Article in Molecular neurobiology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.
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Who cites it
2 citing papers in PubMed.
- Neuropathy-Associated HSPB1 Mutant Impairs Neuronal Mechanoadaptation and Axonal Regeneration.Cells · 2026Article
- The GAP43/RAC1 axis drives glycolytic reprogramming and progression in lung adenocarcinoma.Respiratory research · 2026Article
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Authors and funding
9 authors.
Funding
Abstract
Bexarotene is a retinoid X receptor (RXR) pharmacological agonist that has been demonstrated to treat cutaneous T-cell lymphoma and promising therapeutic potential for neurological diseases. But it still remains unclear whether bexarotene participates in regulation of neuroblastoma. Human neuroblastoma SH-SY5Y cells were used as a model to investigate the neuronal differentiation impact of bexarotene. Bexarotene-cultured SH-SY5Y cells showed changes in cell morphology, adopting pyramidal shapes and extending neurites, increased expression of neuronal marker β-tubulin III and mature neurons marker neurofilament M and upregulation of neuronal differentiation markers including growth-associated protein 43 (GAP43) and synaptophysin (SYP). SH-SY5Y cells induced by bexarotene increased the expression of GABAergic marker glutamate decarboxylase (GAD1) and dopaminergic marker TH, but not glutamatergic marker glutamate-ammonia ligase (GLUL) and cholinergic marker solute carrier family 18 member 1 (SLC18A1). Functional enrichment analysis of RNAseq data and subsequent cell experiments revealed that the PI3K-Akt axis is the dominant signaling pathway promoting the differentiation of SH-SY5Y cells into mature and functional neurons in response to bexarotene. Additionally, we observed that SH-SY5Y cells show reduced proliferation rates accompanied by decreased expression of cyclin-dependent kinase 6 (CDK6) and increased expression of cyclin-dependent kinase 1 (CDK1) following 7-day exposure to bexarotene, suggesting bexarotene induces a quiescent state in SH-SY5Y cells. SH-SY5Y cells can be induced to mature neurons with decreased proliferation induced by bexarotene via PI3K-Akt axis. It indicates bexarotene has the potential to treat neuroblastoma.
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Registered trials
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