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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

Growth Inhibitory Effects of Dipotassium Glycyrrhizinate in Glioblastoma Cell Lines by Targeting MicroRNAs Through the NF-kappa B Signaling Pathway

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Author(s):
Bonafe, Gabriel Alves [1] ; dos Santos, Jessica Silva [1] ; Ziegler, Jussara Vaz [2] ; Umezawa, Kazuo [3] ; Ribeiro, Marcelo Lima [4] ; Rocha, Thalita [2] ; Ortega, Manoela Marques [1]
Total Authors: 7
Affiliation:
[1] USF, Lab Cell & Mol Tumor Biol & Bioact Cpds, Post Grad Program Hlth Sci, Braganca Paulista, SP - Brazil
[2] USF, Multidisciplinary Res Lab, Post Grad Program Hlth Sci, Braganca Paulista, SP - Brazil
[3] Aichi Med Univ, Dept Mol Target Med, Sch Med, Nagakute, Aichi - Japan
[4] USF, Clin Pharmacol & Gastroenterol Unit, Post Grad Program Hlth Sci, Braganca Paulista, SP - Brazil
Total Affiliations: 4
Document type: Journal article
Source: FRONTIERS IN CELLULAR NEUROSCIENCE; v. 13, MAY 28 2019.
Web of Science Citations: 0
Abstract

It has been shown that nuclear factor kappa-B (NF-kappa B) is constitutively activated in glioblastoma (GBM), suggesting that the pathway could be a therapeutic target. Glycyrrhetic acid (GA), a compound isolated from licorice (Glycyrrhiza glabra), has bee n shown to decrease cell viability and increases apoptosis in human cancer cell lines by NF-kappa B signaling pathway suppression. Dipotassium glycyrrhizinate (DPG), a dipotassium salt of GA, has anti-inflammatory properties without toxicity. The current study examined the effectiveness of DPG as an anti-tumor in U87MG and T98G GBM cell lines. Additionally, we assessed DPG as a candidate for combinational therapy in GBM with temozolomide (TMZ). Our results demonstrated that the viability of U87MG and T98G cells significantly decreased in a time- and dose-dependent manner after DPG treatment, and the apoptotic ratio of DPG-treated groups was significantly higher than that of control groups. In addition, DPG in combination with TMZ revealed synergistic effects. Furthermore, the expression of NF-kappa B-luciferasereporter in transfected GBM cell lines was remarkably reduced after DPG exposure by up-regulating miR16 and miR146a, which down-regulate its target genes, IRAK2 and TRAF6. A reduced neuro-sphere formation was also observed after DPG in both GBM cells. In conclusion, DPG presented anti-tumoral effect on GBM cell lines through a decrease on proliferation and an increase on apoptosis. In addition, our data also suggest that DPG anti-tumoral effect is related to NF-kappa B suppression, where IRAK2- and TRAF6-mediating miR16 and miF?146a, respectively, might be a potential therapeutic target of DPG. (AU)

FAPESP's process: 15/03870-1 - Identification of single-nucleotide polymorphisms in microRNAs involved with the glioblastoma susceptibility
Grantee:Manoela Marques Ortega
Support type: Regular Research Grants
FAPESP's process: 17/03064-0 - Dipotassium Glycyrrhizinate effect on the expression of microRNAs associated with the NF-kB pathway in glioblastoma multiforme cell lines
Grantee:Gabriel Alves Bonafé
Support type: Scholarships in Brazil - Scientific Initiation