Bottom up proteomics reveals novel differentiation proteins in neuroblastoma cells treated with 13-cis retinoic acid

Halakos, Effie G.; Connell, Andrew J.; Glazewski, Lisa; Wei, Shuo; Mason, Robert W.

doi:10.1016/j.jprot.2019.103491

Cited by 5 publications

(4 citation statements)

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“…There were high overlaps of the identified peptides and proteins between two TMT data sets (Figure S3B, Proteomics experiments, related Figure 2), supporting the validity of proteomic experiments. Compared to the previous proteome profile (3,333 proteins and 5,593 proteins from SK-N-SH cells) (Halakos et al, 2019;Li et al, 2018) and phosphoproteome profile (15,417 phosphopeptides from SK-N-BE2 cells) (Scaturro et al, 2018) obtained from neuroblastoma cells, our data represent a more comprehensive neuroblastoma proteome (Figures 2B and 2C) and phosphoproteome for the identification of protein signatures associated with topotecan resistance under serum starvation.…”

Section: Quantitative Proteomic Profiling Of Sk-n-sh Cellsmentioning

confidence: 70%

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DNA repair and cholesterol-mediated drug efflux induce dose-dependent chemoresistance in nutrient-deprived neuroblastoma cells

et al. 2021

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Summary Neuroblastoma is a solid, heterogeneous pediatric tumor. Chemotherapy is widely used to treat neuroblastoma. However, dose-dependent responses and chemoresistance mechanisms of neuroblastoma cells to anticancer drugs remain challenging. Here, we investigated the dose-dependent effects of topotecan on human neuroblastoma cells (SK-N-SH, SH-SY5Y, and SK-N-BE) under various nutrient supply conditions. Serum-starved human neuroblastoma cells showed reduced toxicity. Their survival rate increased upon treatment with a high concentration (1 μM) of topotecan. Quantitative profiling of global and phosphoproteome identified 12,959 proteins and 48,812 phosphosites, respectively, from SK-N-SH cells. Network analysis revealed that topotecan upregulated DNA repair and cholesterol-mediated topotecan efflux, resulting in topotecan resistance. Results of DNA damage assay, cell cycle, and quantitative analyses of membrane cholesterol supported the validity of these resistance factors and their applicability to all neuroblastoma cells. Our results provide a model for high dose-dependent chemoresistance in neuroblastoma cells that could enable a patient-dependent chemotherapy screening strategy.

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Section: Quantitative Proteomic Profiling Of Sk-n-sh Cellsmentioning

confidence: 70%

“…The treatment outcome for high-risk neuroblastoma has also been improved with intensive multimodal treatment. However, a substantial number of patients still experience relapse or progression (Herd et al, 2019;Morgenstern et al, 2013).…”

Section: Introductionmentioning

confidence: 99%

DNA repair and cholesterol-mediated drug efflux induce dose-dependent chemoresistance in nutrient-deprived neuroblastoma cells

et al. 2021

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“…The basic principle is that 13-cis RA induces residual tumor cell differentiation and reduces the risk of recurrence after chemotherapy, surgical excision, and bone marrow transplantation in patients. However, the mechanism has not been fully elucidated [ 7 ]. MYCN amplification (MNA) has been reported in approximately 25% of patients diagnosed with neuroblastoma, and MYCN amplification affected cell differentiation procedures.…”

Section: Introductionmentioning

confidence: 99%

Chlorogenic Acid Induced Neuroblastoma Cells Differentiation via the ACAT1-TPK1-PDH Pathway

et al. 2023

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Background: Chlorogenic acid (CHA) has been shown to have substantial biological activities, including anti-inflammatory, antioxidant, and antitumor effects. However, the pharmacological role of CHA in neuroblastoma has not yet been assessed. Neuroblastoma is a type of cancer that develops in undifferentiated sympathetic ganglion cells. This study aims to assess the antitumor activity of CHA against neuroblastoma and reveal its mechanism of action in cell differentiation. Methods: Be(2)-M17 and SH-SY5Y neuroblastoma cells were used to confirm the differentiation phenotype. Subcutaneous and orthotopic xenograft mouse models were also used to evaluate the antitumor activity of CHA. Seahorse assays and metabolomic analyses were further performed to investigate the roles of CHA and its target ACAT1 in mitochondrial metabolism. Results: CHA induced the differentiation of Be(2)-M17 and SH-SY5Y neuroblastoma cells in vivo and in vitro. The knockdown of mitochondrial ACAT1, which was inhibited by CHA, also resulted in differentiation characteristics in vivo and in vitro. A metabolomic analysis revealed that thiamine metabolism was involved in the differentiation of neuroblastoma cells. Conclusions: These results provide evidence that CHA shows good antitumor activity against neuroblastoma via the induction of differentiation, by which the ACAT1-TPK1-PDH pathway is involved. CHA is a potential drug candidate for neuroblastoma therapy.

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“…Neuroblastoma (NB), which results from the improper differentiation of neural crest progenitors, is the 2 nd most frequent extracranial pediatric cancer, 1 accounting for about 10% of all malignancies in children and 15% of all cancerrelated deaths in this population. 2,3 Although new treatment options constantly emerge over the past years, the long-term overall survival (OS) of high-risk NB is still below 50%.…”

Section: Introductionmentioning

confidence: 99%

Arsenic trioxide induces the differentiation of retinoic acid-resistant neuroblastoma cells via upregulation of HoxC9

Li¹,

Feng²,

Chen³

et al. 2022

Adv Clin Exp Med

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Background. Neuroblastoma (NB) is one of the most common extracranial tumors with limited therapeutic options. Retinoic acid (RA) has been identified to play anticancer role against NB cells by inducing the differentiation and apoptosis of immature neuroblasts. However, silencing HoxC9 promoter by EZH2-induced H3K27me3 hypermethylation can lead to RA resistance. Previous studies have suggested that arsenic trioxide (ATO), an inhibitor of DNA methylation, could downregulate the expression of EZH2 in breast cancer cells.Objectives. In our study, we attempted to obtain some insight into the mechanisms of differentiation of RA-resistant NB cells by detecting the expressions of HoxC9 and EZH2 in NB cells treated with ATO, so as to provide a basis for the subsequent treatment of RA-resistant NB by ATO. Materials and methods.Two NB cell lines, SK-N-AS (retinoic acid-resistant neuroblastoma cells) and SK-N-SH (retinoic acid-sensitive neuroblastoma cells), were used in our experiments. Cell proliferation and apoptosis were respectively determined with Cell Counting Kit-8 (CCK-8) assay kit and Annexin V staining. The inverted phase contrast microscope was used to observe cell growth and measure the total length of nerve synapses. We employed label-free quantitative proteomic analysis to profile ATO-dependent changes in the proteome of NB cells. Western blot was used to detect the expressions of HoxC9, HoxD8 and EZH2.Results. Arsenic trioxide inhibited the cell proliferation and increased apoptosis and total length of synapses in two NB cell lines. The expressions of HoxC9 and HoxD8 were upregulated, while the expression of EZH2 was downregulated in the SK-N-AS cell line. No significant changes in the 3 proteins mentioned above were observed in the SK-N-SH cell line after ATO treatment.Conclusions. Arsenic trioxide may reactivate the expression of HoxC9 by downregulating EZH2, which leads to restoring RA sensitivity and promoting the differentiation and apoptosis of RA-resistant NB cells.

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Bottom up proteomics reveals novel differentiation proteins in neuroblastoma cells treated with 13-cis retinoic acid

Cited by 5 publications

References 123 publications

DNA repair and cholesterol-mediated drug efflux induce dose-dependent chemoresistance in nutrient-deprived neuroblastoma cells

DNA repair and cholesterol-mediated drug efflux induce dose-dependent chemoresistance in nutrient-deprived neuroblastoma cells

Chlorogenic Acid Induced Neuroblastoma Cells Differentiation via the ACAT1-TPK1-PDH Pathway

Arsenic trioxide induces the differentiation of retinoic acid-resistant neuroblastoma cells via upregulation of HoxC9

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