Changes in Gene Expression Profiling of Apoptotic Genes in Neuroblastoma Cell Lines upon Retinoic Acid Treatment

Celay, Jon; Blanco, Idoia; Lázcoz, Paula; Rotinen, Mirja; Castresana, Javier S.; Encı́o, Ignacio

doi:10.1371/journal.pone.0062771

Cited by 16 publications

(19 citation statements)

References 39 publications

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“…Celay et al noted variations in apoptosis in neuroblastoma cell lines that were treated with all- trans - retinoic acid (ATRA) that were not only cell line dependent, but also time dependent. In their study, the SK-N-BE(2) cell line took up to nine days of treatment before showing significant changes in TUNEL assay and the SH-SY5Y cell line showed no change in TUNEL assay even after 9 days of treatment [32]. We had similar results with the SH-SY5Y cell line when cell cycle was studied.…”

Section: Discussionsupporting

confidence: 62%

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Preclinical Evaluation of a Novel RXR Agonist for the Treatment of Neuroblastoma

Waters

Stewart

Atigadda

et al. 2015

Molecular Cancer Therapeutics

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Neuroblastoma remains a common cause of pediatric cancer deaths, especially for children who present with advanced stage or recurrent disease. Currently, retinoic acid therapy is used as maintenance treatment to induce differentiation and reduce tumor recurrence following induction therapy for neuroblastoma, but unavoidable side effects are seen. A novel retinoid, UAB30, has been shown to generate negligible toxicities. In the current study, we hypothesized that UAB30 would have a significant impact on multiple neuroblastoma cell lines in vitro and in vivo. Cellular survival, cell cycle analysis, migration, and invasion were studied using alamarBlue® assays, FACS, and Transwell® assays, respectively, in multiple cell lines following treatment with UAB30. In addition, an in vivo murine model of human neuroblastoma was utilized to study the effects of UAB30 upon tumor xenograft growth and animal survival. We successfully demonstrated decreased cellular survival, invasion and migration, cell cycle arrest and increased apoptosis after treatment with UAB30. Furthermore, inhibition of tumor growth and increased survival was observed in a murine neuroblastoma xenograft model. The results of these in vitro and in vivo studies suggest a potential therapeutic role for the low toxicity synthetic retinoid X receptor selective agonist, UAB30, in neuroblastoma treatment.

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Section: Discussionsupporting

confidence: 62%

“…It has been reported that p53 was upregulated in tumor cells following retinoid treatment and was responsible for cellular differentiation [31, 32]. We investigated p53 expression and found no consistent change by immunoblotting (Supplemental Data Fig.…”

Section: Discussionmentioning

confidence: 91%

Preclinical Evaluation of a Novel RXR Agonist for the Treatment of Neuroblastoma

Waters

Stewart

Atigadda

et al. 2015

Molecular Cancer Therapeutics

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“…Celay et al noted variations in apoptosis in neuroblastoma cell lines that were treated with ATRA that were not only cell line dependent, but also time dependent. In their study, one cell line took up to nine days of treatment before showing changes in TUNEL assay and another cell line showed no change in TUNEL assay even after 9 days of treatment [49]. …”

Section: Discussionmentioning

confidence: 99%

UAB30, a novel RXR agonist, decreases tumorigenesis and leptomeningeal disease in group 3 medulloblastoma patient-derived xenografts

et al. 2018

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“…Indeed, retinoic acid can induce differentiation and apoptosis of neuroblastoma cells. 38,39 Previously, it has been shown that CYLD promotes apoptosis or necrosis by blocking NF-κB signaling activity. 24,40,41 In addition, the NF-κB pathway is generally tightly regulated with a negative feedback loop, for instance, by the induction of SUMO protease SENP2 upon genotoxic stress to attenuate cell survival response.…”

Section: Cyld Expression Is Associated With Clinical Outcomes In Neurmentioning

confidence: 99%

Deubiquitinating activity of CYLD is impaired by SUMOylation in neuroblastoma cells

2014

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CYLD is a deubiquitinating (DUB) enzyme that has a pivotal role in modulating nuclear factor kappa B (NF-κB) signaling pathways by removing the lysine 63-and linear-linked ubiquitin chain from substrates such as tumor necrosis factor receptor-associated factor 2 (TRAF2) and TRAF6. Loss of CYLD activity is associated with tumorigenicity, and levels of CYLD are lost or downregulated in different types of human tumors. In the present study, we found that high CYLD expression was associated with better overall survival and relapse-free neuroblastoma patient outcome, as well as inversely correlated with the stage of neuroblastoma. Retinoic acid-mediated differentiation of neuroblastoma restored CYLD expression and promoted SUMOylation of CYLD. This posttranslational modification inhibited deubiquitinase activity of CYLD against TRAF2 and TRAF6 and facilitated NF-κB signaling. Overexpression of non-SUMOylatable mutant CYLD in neuroblastoma cells reduced retinoic acid-induced NF-κB activation and differentiation of cells, but instead promoted cell death.

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Changes in Gene Expression Profiling of Apoptotic Genes in Neuroblastoma Cell Lines upon Retinoic Acid Treatment

Cited by 16 publications

References 39 publications

Preclinical Evaluation of a Novel RXR Agonist for the Treatment of Neuroblastoma

Preclinical Evaluation of a Novel RXR Agonist for the Treatment of Neuroblastoma

UAB30, a novel RXR agonist, decreases tumorigenesis and leptomeningeal disease in group 3 medulloblastoma patient-derived xenografts

Deubiquitinating activity of CYLD is impaired by SUMOylation in neuroblastoma cells

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