Abstract

BackgroundSchwannoma arising from peripheral nervous sheaths is a benign tumor.MethodsTo evaluate cell cytotoxicity, (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) tetrazolium reduction and terminal deoxynucleotidyltransferase UTP nick-end labeling (TUNEL) assays were used. A microRNA (miRNA) array was used to identify the miRNAs involved in curcumin-induced apoptosis. To examine miRNA expression, quantitative RT-PCR was used.ResultsIn this study, curcumin exerted cellular cytotoxicity against RT4 schwannoma cells, with an increase in TUNEL-positive cells. Curcumin also activated the expression of apoptotic proteins, such as polyADP ribose polymerase, caspase-3, and caspase-9. The miRNA array revealed that seven miRNAs (miRNA 350, miRNA 17-2-3p, let 7e-3p, miRNA1224, miRNA 466b-1-3p, miRNA 18a-5p, and miRNA 322-5p) were downregulated following treatment with both 10 and 20 μM curcumin in RT4 cells, while four miRNAs (miRNA122-5p, miRNA 3473, miRNA182, and miRNA344a-3p) were upregulated. Interestingly, transfection with a miRNA 344a-3p mimic downregulated the mRNA expression of Bcl2 and upregulated that of Bax, Curcumin treatment in RT 4 cells also reduced the mRNA expression of Bcl2 and enhanced expression of Bax, Overexpression of miRNA344a-3p mimic combined with curcumin treatment activated the expression of apoptotic proteins, including procaspase-9 and cleaved caspase-3 while inhibition of miRNA 344a-3p using miR344a-3p inhibitor repressed cleaved caspase-3 and -9 in curcumin treated RT-4 cells compared to control.ConclusionsOur findings demonstrate that curcumin induces apoptosis in schwannoma cells via miRNA 344a-3p. Thus, curcumin may serve as a potent therapeutic agent for the treatment of schwannoma.

Highlights

  • Schwannoma arising from peripheral nervous sheaths is a benign tumor

  • Curcumin was cytotoxic to RT4 schwannoma cells in a dose-dependent manner (Fig. 1a)

  • Western blot analysis revealed that curcumin treatment in RT4 cells activated apoptotic markers, such as cleaved caspase-3 and attenuated procaspase-3, -9 and proPARP (Fig. 1c) To determine whether curcumin induces apoptosis, a terminal deoxynucleotidyltransferase UTP nick-end labeling (TUNEL) assay was performed

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Summary

Introduction

Schwannoma arising from peripheral nervous sheaths is a benign tumor. Schwannoma arising from peripheral nervous sheaths originates from the neuroectoderm and myelin-forming Schwann cells [1]. Schwannomas originate from the vestibular nerve and are accompanied by hearing loss and neurological disorders [2,3,4]. Neurofibromatosis 2 (NF2) results from loss of the NF2 gene, which encodes the Merlin protein [5]. Curcumin, derived from the spice turmeric (Curcuma longa), is a non-flavonoid polyphenol. Curcumin has multiple biological activities, such as anti-inflammatory activity [7], anti-bacterial action [8], and anti-oxidant properties [9]. Curcumin exhibits neuroprotective effects in Huntington’s [10] and Alzheimer’s [11] diseases.

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