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Objective:Glioblastoma is an invasive tumor of the central nervous system. Epigenetic therapy of cancer is potentially very useful in reversing some of cancer defects due to reversibility of epigenetic alterations. MEG3 is a tumor suppressor long non-coding RNA (lncRNA) that expresses in the majority of normal tissues. Methylation of the MEG3 promoter region elicits a decrease in its expression in glioblastoma cells. Bioactive nutrients including curcumin offer great potential in altering DNA methylation status. Herein, we aim to investigate the epigenetic-based role of dendrosomal-curcumin (DNC) in upregulation of MEG3 expression in glioblastoma cells. Methods: We evaluated DNC entrance to U87MG cells with the use of the fluorescent characteristics of curcumin. Next we performed the MTT assay to evaluate DNC and dendrosome effects on cell viability. The ability of DNC to boost expression of MEG3 in DNA methylation regulation was accomplished by a study of the relative expressions of MEG3 and DNA methylation regulator enzymes, DNA methyltransferases (DNMT1, DNMT3A and 3B)  using semi-quantitative and quantitative PCR. Results: We observed the entrance of DNC into U87MG cells. DNC significantly caused U87MG cell death in a time and dose-dependent manner. However dendrosome did not show any toxic effect on this cell line. Data acquired from gene expression assays determined that DNC upregulated MEG3 expression (P<0.05) and downregulated DNMT3B expression (P<0.05). There was no significant effect on DNMT1, 3A expression in U87MG cells. Conclusion: The data showed that DNC could awaken epigenetically silenced tumor suppressor genes through an ambiguous route in glioblastoma cells. Notwithstanding, DNA hypomethylation has occurred by downregulation of DNMTs, inactive DNA demethylation and or active demethylation, subsequently tumor suppressor genes such as MEG3 a cell growth regulator overexpressed. We concluded that DNC has useful characteristics in epigenetic therapy of glioblastoma.

Keywords: MEG3, Epigenetic, Glioblastoma, DNC, MEG3, DNMT

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