| Full text | |
| 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 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 |