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

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]

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

• 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 Opportunities: 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 Opportunities: Scholarships in Brazil - Scientific Initiation