ArticleCell death & disease2013
Differential effect of long-term drug selection with doxorubicin and vorinostat on neuroblastoma cells with cancer stem cell characteristics.
Article in Cell death & disease, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed, 41 citations in OpenAlex.
- Amniotic membrane promotes doxorubicin potency by suppressing SH-SY5Y neuroblastoma cell angiogenesis.BMC cancer · 2025Article
- Proteomic-based stemness score measures oncogenic dedifferentiation and enables the identification of druggable targets.Cell genomics · 2025Article
- Three-Dimensional Culture Systems in Neuroblastoma Research.Organoids · 2025Article
- Development and validation of a novel stemness-related prognostic model for neuroblastoma using integrated machine learning and bioinformatics analyses.Translational pediatrics · 2024Article
- UBE4B interacts with the ITCH E3 ubiquitin ligase to induce Ku70 and c-FLIPL polyubiquitination and enhanced neuroblastoma apoptosis.Cell death & disease · 2023Article
- Recent Advances in Molecular and Cellular Functions of S100A10.Biomolecules · 2023Review
- Methylation-based reclassification and risk stratification of skull-base chordomas.Frontiers in oncology · 2022Article
- Mechanisms involved in selecting and maintaining neuroblastoma cancer stem cell populations, and perspectives for therapeutic targeting.World journal of stem cells · 2021Review
- Broad-Spectrum HDAC Inhibitors Promote Autophagy through FOXO Transcription Factors in Neuroblastoma.Cells · 2021Article
- Article
- Review
- Effects of PI3K and FGFR inhibitors alone and in combination, and with/without cytostatics in childhood neuroblastoma cell lines.International journal of oncology · 2021Article
- Integrated Transcriptomic Analysis Revealed Hub Genes and Pathways Involved in Sorafenib Resistance in Hepatocellular Carcinoma.Pathology oncology research : POR · 2021Article
- Histone Deacetylases and Histone Deacetylase Inhibitors in Neuroblastoma.Frontiers in cell and developmental biology · 2020Review
- Cancer stem cells in neuroblastoma therapy resistance.Cancer drug resistance (Alhambra, Calif.) · 2019Article
- Discovery, characterization and potential roles of a novel NF-YAx splice variant in human neuroblastoma.Journal of experimental & clinical cancer research : CR · 2019Article
- GX15-070 (Obatoclax), a Bcl-2 family proteins inhibitor engenders apoptosis and pro-survival autophagy and increases Chemosensitivity in neuroblastoma.BMC cancer · 2019Article
- Integrative analysis of gene expression and DNA methylation through one-class logistic regression machine learning identifies stemness features in medulloblastoma.Molecular oncology · 2019Article
- Cancer Stem Cells in Neuroblastoma: Expanding the Therapeutic Frontier.Frontiers in molecular neuroscience · 2019Review
- Doxorubicin-provoked increase of mitotic activity and concomitant drain of G0-pool in therapy-resistant BE(2)-C neuroblastoma.PloS one · 2018Article
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Authors and funding
10 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Numerous studies have confirmed that cancer stem cells (CSCs) are more resistant to chemotherapy; however, there is a paucity of data exploring the effect of long-term drug treatment on the CSC sub-population. The purpose of this study was to investigate whether long-term doxorubicin treatment could expand the neuroblastoma cells with CSC characteristics and histone acetylation could affect stemness gene expression during the development of drug resistance. Using n-myc amplified SK-N-Be(2)C and non-n-myc amplified SK-N-SH human neuroblastoma cells, our laboratory generated doxorubicin-resistant cell lines in parallel over 1 year; one cell line intermittently treated with the histone deacetylase inhibitor (HDACi) vorinostat and the other without exposure to HDACi. Cells' sensitivity to chemotherapeutic drugs, the ability to form tumorspheres, and capacity for in vitro invasion were examined. Cell-surface markers and side populations (SPs) were analyzed using flow cytometry. Differentially expressed stemness genes were identified through whole genome analysis and confirmed with real-time PCR. Our results indicated that vorinostat increased the sensitivity of only SK-N-Be(2)C-resistant cells to chemotherapy, made cells lose the ability to form tumorspheres, and reduced in vitro invasion and the SP percentage. CD133 was not enriched in doxorubicin-resistant or vorinostat-treated doxorubicin-resistant cells. Nine stemness-linked genes (ABCB1, ABCC4, LMO2, SOX2, ERCC5, S100A10, IGFBP3, TCF3, and VIM) were downregulated in vorinostat-treated doxorubicin-resistant SK-N-Be(2)C cells relative to doxorubicin-resistant cells. A sub-population of cells with CSC characteristics is enriched during prolonged drug selection of n-myc amplified SK-N-Be(2)C neuroblastoma cells. Vorinostat treatment affects the reversal of drug resistance in SK-N-Be(2)C cells and may be associated with downregulation of stemness gene expression. This work may be valuable for clinicians to design treatment protocols specific for different neuroblastoma patients.
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