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4-Hydroxychalcone Induces Cell Death Via Oxidative Stress in -Amplified Human Neuroblastoma Cells

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Publisher Wiley
Date 2019 Dec 31
PMID 31885773
Citations 2
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Abstract

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 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 -amplified IMR-32 and SK-N-BE (2) neuroblastoma cells, when compared to non--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 -amplified human neuroblastoma cells, which rationalizes its further study in the development of new therapies for pediatric neuroblastoma.

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References
1.
Oh G, Kim H, Shen A, Lee S, Khadka D, Pandit A . Cisplatin-induced Kidney Dysfunction and Perspectives on Improving Treatment Strategies. Electrolyte Blood Press. 2015; 12(2):55-65. PMC: 4297704. DOI: 10.5049/EBP.2014.12.2.55. View

2.
Orlikova B, Tasdemir D, Golais F, Dicato M, Diederich M . The aromatic ketone 4'-hydroxychalcone inhibits TNFα-induced NF-κB activation via proteasome inhibition. Biochem Pharmacol. 2011; 82(6):620-31. DOI: 10.1016/j.bcp.2011.06.012. View

3.
Adhikary S, Eilers M . Transcriptional regulation and transformation by Myc proteins. Nat Rev Mol Cell Biol. 2005; 6(8):635-45. DOI: 10.1038/nrm1703. View

4.
Liu G, Ge Z, Zhao M, Zhou Y . Design, synthesis and cytotoxic activities of novel aliphatic amino-substituted flavonoids. Molecules. 2013; 18(11):14070-84. PMC: 6270462. DOI: 10.3390/molecules181114070. View

5.
Mlakar V, Jurkovic Mlakar S, Lesne L, Marino D, Rathi K, Maris J . PRIMA-1-induced neuroblastoma cell death is modulated by p53 and mycn through glutathione level. J Exp Clin Cancer Res. 2019; 38(1):69. PMC: 6373164. DOI: 10.1186/s13046-019-1066-6. View