scholarly journals Reactive Oxygen Species Regulate the Levels of Dual Oxidase (Duox1-2) in Human Neuroblastoma Cells

PLoS ONE ◽  
2012 ◽  
Vol 7 (4) ◽  
pp. e34405 ◽  
Author(s):  
Simona Damiano ◽  
Roberta Fusco ◽  
Annalisa Morano ◽  
Mariarosaria De Mizio ◽  
Roberto Paternò ◽  
...  
2019 ◽  
Vol 2019 ◽  
pp. 1-16 ◽  
Author(s):  
Amnah M. Alshangiti ◽  
Eszter Tuboly ◽  
Shane V. Hegarty ◽  
Cathal M. McCarthy ◽  
Aideen M. Sullivan ◽  
...  

Neuroblastoma is an embryonal malignancy that arises from cells of sympathoadrenal lineage during the development of the nervous system. It is the most common pediatric extracranial solid tumor and is responsible for 15% of childhood deaths from cancer. Fifty percent of cases are diagnosed as high-risk metastatic disease with a low overall 5-year survival rate. More than half of patients experience disease recurrence that can be refractory to treatment. Amplification of the MYCN gene is an important prognostic indicator that is associated with rapid disease progression and a poor prognosis, highlighting the need for new therapeutic approaches. In recent years, there has been an increasing focus on identifying anticancer properties of naturally occurring chalcones, which are secondary metabolites with variable phenolic structures. Here, we report that 4-hydroxychalcone is a potent cytotoxin for MYCN-amplified IMR-32 and SK-N-BE (2) neuroblastoma cells, when compared to non-MYCN-amplified SH-SY5Y neuroblastoma cells and to the non-neuroblastoma human embryonic kidney cell line, HEK293t. Moreover, 4-hydroxychalcone treatment significantly decreased cellular levels of the antioxidant glutathione and increased cellular reactive oxygen species. In addition, 4-hydroxychalcone treatment led to impairments in mitochondrial respiratory function, compared to controls. In support of this, the cytotoxic effect of 4-hydroxychalcone was prevented by co-treatment with either the antioxidant N-acetyl-L-cysteine, a pharmacological inhibitor of oxidative stress-induced cell death (IM-54) or the mitochondrial reactive oxygen species scavenger, Mito-TEMPO. When combined with the anticancer drugs cisplatin or doxorubicin, 4-hydroxychalcone led to greater reductions in cell viability than was induced by either anti-cancer agent alone. In summary, this study identifies a cytotoxic effect of 4-hydroxychalcone in MYCN-amplified human neuroblastoma cells, which rationalizes its further study in the development of new therapies for pediatric neuroblastoma.


2011 ◽  
Vol 313 (2) ◽  
pp. 201-210 ◽  
Author(s):  
Qi Zhang ◽  
Yan Ma ◽  
Yue-Fang Cheng ◽  
Wen-Jie Li ◽  
Zhenzhong Zhang ◽  
...  

Life Sciences ◽  
1997 ◽  
Vol 60 (21) ◽  
pp. 1905-1914 ◽  
Author(s):  
Jonne Naarala ◽  
Pirkko Tervo ◽  
Jarkko Loikkanen ◽  
Kai Savolainen

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 782.2-782
Author(s):  
C. H. Lee ◽  
C. H. Chung ◽  
Y. J. Choi ◽  
W. H. Yoo ◽  
J. Y. Kim ◽  
...  

Background:Reactive oxygen species (ROS) are one of the significant factors of chemical or physical cell signaling in a wide variety of cell types including skeletal cells. Receptor activator of NF-βB ligand (RANKL) induces generation of intracellular ROS, which act as second messengers in RANKL-mediated osteoclastogenesis. Dual oxidase maturation factor 1 (Duoxa1) was first identified as aDrosophilaNumb-interacting protein (NIP), and has been associated with the maturation of ROS generating enzymes including dual oxidases (Duox1 and Duox2). In the progression of osteoclast differentiation using mouse bone marrow-derived macrophages (BMMs), we identified that only Duoxa1 level showed an effective change upon RANKL stimulation, but not Duox1, Duox2, and Duoxa2.Objectives:we hypothesized that Duoxa1 could independently act as a second messenger for RANKL stimulation and regulate ROS production during osteoclast differentiation.Methods:Using siRNA or retrovirus transduction and knockdown of Duoxa1 via siRNAResults:Duoxa1 level gradually increased during RANKL-induced osteoclast differentiation. We found that Duoxa1 regulated RANKL-stimulated osteoclast formation and bone resorption positively. knockdown of Duoxa1 via siRNA decreased the RANKL-induced ROS production. During Duoxa1-related control of osteoclastogenesis, activation of tumor necrosis factor receptor (TNFR)-associated factor 6 (TRAF6)-mediated early signaling molecules including MAPKs, Akt, IβB, Btk, and PLC 2 was affected, which sequentially modified the mRNA or protein expression levels of key transcription factors in osteoclastogenesis, such as c-Fos and NFATc1, as well as mRNA expression of osteoclast-specific markers including OSCAR, ATP6v0d2, and CtsK.Conclusion:Overall, our data indicate that Duoxa1 plays a crucial role in osteoclastogenesis via regulating RANKL-induced intracellular ROS production and activating TRAF6-mediated signaling.Disclosure of Interests:None declared


2018 ◽  
Vol 38 (1) ◽  
Author(s):  
Chol Seung Lim ◽  
Jung-Soo Han

Activity of neprilysin (NEP), the major protease which cleaves amyloid-β peptide (Aβ), is reportedly reduced in the brains of patients with Alzheimer’s disease (AD). Accumulation of Aβ generates reactive oxygen species (ROS) such as 4-hydroxynonenal (HNE), and then reduces activities of Aβ-degrading enzymes including NEP. Xanthorrhizol (Xan), a natural sesquiterpenoid, has been reported to possess antioxidant and anti-inflammatory properties. The present study examined the effects of Xan on HNE- or oligomeric Aβ42-induced oxidative modification of NEP protein. Xan was added to the HNE- or oligomeric Aβ42-treated SK-N-SH human neuroblastoma cells and then levels, oxidative modification and enzymatic activities of NEP protein were measured. Increased HNE levels on NEP proteins and reduced enzymatic activities of NEP were observed in the HNE- or oligomeric Aβ42-treated cells. Xan reduced HNE levels on NEP proteins and preserved enzymatic activities of NEP in HNE- or oligomeric Aβ42-treated cells. Xan reduced Aβ42 accumulation and protected neurones against oligomeric Aβ42-induced neurotoxicity through preservation of NEP activities. These findings indicate that Xan possesses therapeutic potential for the treatment of neurodegenerative diseases, including AD, and suggest a potential mechanism for the neuroprotective effects of antioxidants for the prevention of AD.


Antioxidants ◽  
2020 ◽  
Vol 9 (1) ◽  
pp. 50 ◽  
Author(s):  
Silvana Alfei ◽  
Barbara Marengo ◽  
Cinzia Domenicotti

Etoposide (ETO) is a cytotoxic drug that exerts its effect by increasing reactive oxygen species (ROS) production. Although ETO is widely used, fast metabolism, poor solubility, systemic toxicity, and multi-drug resistance induction all limit its administration dosage and its therapeutic efficiency. In order to address these issues, a biodegradable dendrimer was prepared for entrapping and protecting ETO and for enhancing its solubility and effectiveness. The achieved dendrimer complex with ETO (CPX 5) showed the typical properties of a well-functioning delivery system, i.e., nanospherical morphology (70 nm), optimal Z-potential (−45 mV), good drug loading (37%), very satisfying entrapment efficiency (53%), and a remarkably improved solubility in biocompatible solvents. In regards to its cytotoxic activity, CPX 5 was tested on neuroblastoma (NB) cells with very promising results. In fact, the dendrimer scaffold and ETO are able to exert per se a cytotoxic and pro-oxidant activity on human NB cells. When CPX 5 is combined with ETO, it shows a synergistic action, slowly releasing the drug over time and significantly improving and protracting bioactivity. On the basis of these findings, the prepared ETO reservoir represents a novel biodegradable and promising device for the delivery of ETO into NB cells.


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