Influence of LOX/COX inhibitors on cell differentiation induced by all-trans retinoic acid in neuroblastoma cell lines

Rédová, Martina; Chlapek, Petr; Loja, Tomáš; Zitterbart, Karel; Hermanová, Markéta; Štěrba, Jaroslav; Veselská, Renata

doi:10.3892/ijmm_00000341

Cited by 7 publications

(2 citation statements)

References 47 publications

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“…Lipoxygenase (LOX) pathway inhibition enhanced the pro-differentiation action of RA. Co-treatment of ATRA with caffeic acid or celecoxib-LOX and cyclooxygenase 2 (COX2) inhibitors-increased the expression of mature neuronal markers NF-200 and NeuN in MNA SK-N-BE(2) cells [50]. Interestingly, those cotreatments resulted in the decreased expression of NeuN marker in non-MNA SHSY5Y line.…”

Section: Drugs Activating the Cellular Cascades That Potentiate Ra Efmentioning

confidence: 99%

Differentiating Neuroblastoma: A Systematic Review of the Retinoic Acid, Its Derivatives, and Synergistic Interactions

Bayeva¹,

Coll²,

Piskareva

2021

JPM

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A neuroblastoma (NB) is a solid paediatric tumour arising from undifferentiated neuronal cells. Despite the recent advances in disease management and treatment, it remains one of the leading causes of childhood cancer deaths, thereby necessitating the development of new therapeutic agents and regimens. Retinoic acid (RA), a vitamin A derivative, is a promising agent that can induce differentiation in NB cells. Its isoform, 13-cis RA or isotretinoin, is used in NB therapy; however, its effectiveness is limited to treating a minimal residual disease as maintenance therapy. As such, research focuses on RA derivatives that might increase the anti-NB action or explores the potential synergy between RA and other classes of drugs, such as cellular processes mediators, epigenetic modifiers, and immune modulators. This review summarises the in vitro, in vivo, and clinical data of RA, its derivatives, and synergising compounds, thereby establishing the most promising RA derivatives and combinations of RA for further investigation.

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Section: Drugs Activating the Cellular Cascades That Potentiate Ra Efmentioning

confidence: 99%

Differentiating Neuroblastoma: A Systematic Review of the Retinoic Acid, Its Derivatives, and Synergistic Interactions

Bayeva¹,

Coll²,

Piskareva

2021

JPM

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“…Combinations of all-trans retinoic acid (ATRA) with several natural compounds, kinase inhibitors, chemotherapeutics, and proteasome inhibitors have demonstrated additive or synergistic effects [21]. Our research group described the enhancement of the antineoplastic effect of ATRA caused by inhibition of its catabolism using LOX/COX inhibitors (caffeic acid and celecoxib) in neuroblastoma, medulloblastoma, and osteosarcoma cell lines [22][23][24][25]. The benefits of combined treatment in the therapy of several solid tumors have also been confirmed for retinoic acid and other differentiation inducers, such as calcitriol [26][27][28].…”

Section: Introductionmentioning

confidence: 99%

Enhanced Antiproliferative Effect of Combined Treatment with Calcitriol and All-Trans Retinoic Acid in Relation to Vitamin D Receptor and Retinoic Acid Receptor α Expression in Osteosarcoma Cell Lines

Paukovcekova

Valík

Štěrba

et al. 2020

IJMS

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The main objective of this study was to analyze changes in the antiproliferative effect of vitamin D3, in the form of calcitriol and calcidiol, via its combined application with all-trans retinoic acid (ATRA) in osteosarcoma cell lines. The response to treatment with calcitriol and calcidiol alone was specific for each cell line. Nevertheless, we observed an enhanced effect of combined treatment with ATRA and calcitriol in the majority of the cell lines. Although the levels of respective nuclear receptors did not correlate with the sensitivity of cells to these drugs, vitamin D receptor (VDR) upregulation induced by ATRA was found in cell lines that were the most sensitive to the combined treatment. In addition, all these cell lines showed high endogenous levels of retinoic acid receptor α (RARα). Our study confirmed that the combination of calcitriol and ATRA can achieve enhanced antiproliferative effects in human osteosarcoma cell lines in vitro. Moreover, we provide the first evidence that ATRA is able to upregulate VDR expression in human osteosarcoma cells. According to our results, the endogenous levels of RARα and VDR could be used as a predictor of possible synergy between ATRA and calcitriol in osteosarcoma cells.

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Loss of PHF6 leads to aberrant development of human neuron-like cells

Fliedner

Gregor

Ferrazzi

et al. 2020

Sci Rep

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Pathogenic variants in PHD finger protein 6 (PHF6) cause Borjeson–Forssman–Lehmann syndrome (BFLS), a rare X-linked neurodevelopmental disorder, which manifests variably in both males and females. To investigate the mechanisms behind overlapping but distinct clinical aspects between genders, we assessed the consequences of individual variants with structural modelling and molecular techniques. We found evidence that de novo variants occurring in females are more severe and result in loss of PHF6, while inherited variants identified in males might be hypomorph or have weaker effects on protein stability. This might contribute to the different phenotypes in male versus female individuals with BFLS. Furthermore, we used CRISPR/Cas9 to induce knockout of PHF6 in SK-N-BE (2) cells which were then differentiated to neuron-like cells in order to model nervous system related consequences of PHF6 loss. Transcriptome analysis revealed a broad deregulation of genes involved in chromatin and transcriptional regulation as well as in axon and neuron development. Subsequently, we could demonstrate that PHF6 is indeed required for proper neuron proliferation, neurite outgrowth and migration. Impairment of these processes might therefore contribute to the neurodevelopmental and cognitive dysfunction in BFLS.

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Influence of LOX/COX inhibitors on cell differentiation induced by all-trans retinoic acid in neuroblastoma cell lines

Cited by 7 publications

References 47 publications

Differentiating Neuroblastoma: A Systematic Review of the Retinoic Acid, Its Derivatives, and Synergistic Interactions

Differentiating Neuroblastoma: A Systematic Review of the Retinoic Acid, Its Derivatives, and Synergistic Interactions

Enhanced Antiproliferative Effect of Combined Treatment with Calcitriol and All-Trans Retinoic Acid in Relation to Vitamin D Receptor and Retinoic Acid Receptor α Expression in Osteosarcoma Cell Lines

Loss of PHF6 leads to aberrant development of human neuron-like cells

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