Dipotassium Glycyrrhizinate effect on the expression of microRNAs associated with the NF-kB pathway in glioblastoma multiforme cell lines

• Grant number: 17/03064-0
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: May 01, 2017
• End date: December 31, 2017
• Field of knowledge: Biological Sciences - Biochemistry - Molecular Biology
• Principal Investigator: Manoela Marques Ortega
• Grantee: Gabriel Alves Bonafé
• Host Institution: Universidade São Francisco (USF). Campus Bragança Paulista. Bragança Paulista , SP, Brazil

Abstract

Glioblastoma multiforme (GBM) represents about 15-20% of neurological tumors and considered the most aggressive. Biological heterogeneity and resistance to chemotherapy are the largest obstacles to effective treatment of GBM. Several genes and signaling pathways were identified to be responsible for the aggressive phenotype of this tumor; one is the NF-ºB signaling pathway. In mammals, are known five proteins of this family, which belong of two pathways known as canonical and alternative: RelA (p65), RelB, c-Rel, NF-ºB1 (p105/p50) and NF-ºB2 (p100/p52). These proteins form a lot of homodimers and heterodimers inactive by cytoplasmic association with inhibitory proteins. The canonical NF-ºB pathway is the most studied in several tumor types, including GBM, in which it is continuously active causing increased expression of anti-apoptotic genes, survival, adhesion, and cell invasion factors. microRNAs (miRNAs) involved in regulation of NF-ºB pathway are poorly studied in GBM. Recent studies using oral doses of glycyrrhizic acid (GA) showed a reduction of inflammatory process by suppressing the expression of nuclear protein NF-ºB, p65, and by the increase of expression of p53 tumor suppressor protein, and pro-apoptotic proteins caspase-9 and caspase-3 cleaved. Glycyrrhizinate dipotassium (DPG) is a byproduct of GA and is similar to corticosteroids for it anti-inflammatory properties, but without presenting the same side effects. Therefore, the purpose of this study is evaluate the inhibitory effect of DPG on the NF-ºB signaling pathway by modulation of miRNAs previously known to be involved in this pathway in GBM cell lines as a therapeutic target for the disease. (AU)

Scientific publications

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

BONAFE, GABRIEL ALVES; DOS SANTOS, JESSICA SILVA; ZIEGLER, JUSSARA VAZ; UMEZAWA, KAZUO; RIBEIRO, MARCELO LIMA; ROCHA, THALITA; ORTEGA, MANOELA MARQUES. Growth Inhibitory Effects of Dipotassium Glycyrrhizinate in Glioblastoma Cell Lines by Targeting MicroRNAs Through the NF-kappa B Signaling Pathway. FRONTIERS IN CELLULAR NEUROSCIENCE, v. 13, MAY 28 2019. (15/03870-1, 17/03064-0)