Effect of histone deacetylase and proteasome inhibitors in Glioma models

• Grant number: 20/08987-2
• Support Opportunities: Scholarships in Brazil - Doctorate
• Start date: August 01, 2021
• End date: June 30, 2025
• Field of knowledge: Biological Sciences - Pharmacology - Biochemical and Molecular Pharmacology
• Principal Investigator: Leticia Veras Costa Lotufo
• Grantee: Luciana Costa Furtado
• Host Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• Associated research grant: 15/17177-6 - Integrative approach on the sustainable prospection of marine natural products: from diversity to anticancer compounds, AP.BTA.TEM
• Associated scholarship(s): 22/15330-5 - Exploring the involvement of the unfolded protein response (UPR) in proteasome and histone deacetylase inhibitor induced cytotoxicity in glioblastoma, BE.EP.DR

Abstract

Gliomas are tumors of the Central Nervous System that affect mainly the adult population, imposing a low survival rate, and the most frequent type, Glioblastoma, is characterized by high aggressiveness and a poor prognosis. The search for new therapies is essential in order to bring not only more drug options, but also the possibility of innovative treatments, including new therapeutic targets and combined therapies with greater effectiveness and fewer side effects. In this context, Proteasome Inhibitors (PI) and histone deacetylase inhibitors (IHDAC) have been studied in vitro and in vivo Glioma models with promising results. Thus, in the present work, we propose to investigate the promoted effects by proteasome inhibitors (bortezomib, carfilzomib, dihydroeponemycin and marizomib) and histone deacetylase inhibitors (vorinostat and unpublished substances related to PCI-34051) in Glioma models submitted to individual treatment or with the combination of substances. To evaluate the effects, two-dimensional and three-dimensional cell culture models will be used, in addition to the co-culture of astrocytes and Glioma cells. The studies of the mechanisms of action are based on a combined approach of phenotypic and molecular assays evaluating gene expression (real-time PCR and transcriptomics) and protein modulation (western blotting and proteomics) both of the pathways directly related to the targets of the substances (proteasome and HDAC), as well as cell death pathways. (AU)

Scientific publications

(4)

(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)

BAZZANO, CRISTINA F.; DE FELICIO, RAFAEL; ALVES, LUIZ FERNANDO GIOLO; COSTA, JONAS HENRIQUE; ORTEGA, RAQUEL; VIEIRA, BRUNA DOMINGUES; MORAIS-URANO, RAQUEL PERES; FURTADO, LUCIANA COSTA; FERREIRA, EVERTON L. F.; GUBIANI, JULIANA R.; et al. NP³ MS Workflow: An Open-Source Software System to Empower Natural Product-Based Drug Discovery Using Untargeted Metabolomics. Analytical Chemistry, v. 96, n. 19, p. 10-pg., 2024-05-03. (15/01017-0, 19/17721-9, 13/50228-8, 14/10753-9, 15/17177-6, 17/18235-5, 20/08987-2)

NISHIMURA, V, RODOLFO H.; DOS SANTOS, THIAGO; MURIE, VALTER E.; FURTADO, LUCIANA C.; COSTA-LOTUFO, V, LETICIA; CLOSOSKI, GIULIANO C.. Efficient N-arylation of 4-chloroquinazolines en route to novel 4-anilinoquinazolines as potential anticancer agents. Beilstein Journal of Organic Chemistry, v. 17, p. 2968-2975, DEC 22 2021. (15/17177-6, 17/18235-5, 15/21364-6, 18/14150-8, 20/08987-2, 15/01466-9)

VIEIRA, BRUNA DOMINGUES; NIERO, HENRIQUE; DE FELICIO, RAFAEL; ALVES, LUIZ FERNANDO GIOLO; BAZZANO, CRISTINA FREITAS; SIGRIST, RENATA; FURTADO, LUCIANA COSTA; PERSINOTI, GABRIELA FELIX; COSTA-LOTUFO, LETICIA VERAS; TRIVELLA, DANIELA BARRETTO BARBOSA. Production of Epoxyketone Peptide-Based Proteasome Inhibitors by Streptomyces sp. BRA-346: Regulation and Biosynthesis. FRONTIERS IN MICROBIOLOGY, v. 13, p. 17-pg., 2022-03-24. (20/08987-2, 17/18235-5, 19/27306-9, 15/17177-6)

BAUERMEISTER, ANELIZE; FURTADO, LUCIANA COSTA; FERREIRA, ELTHON G.; MOREIRA, EDUARDA ANTUNES; JIMENEZ, PAULA CHRISTINE; LOPES, NORBERTO PEPORINE; ARAUJO, WELINGTON LUIZ; OLCHANHESKI, LUIZ RICARDO; LOTUFO, TITO MONTEIRO DA CRUZ; COSTA-LOTUFO, LETICIA VERAS. Chemical and microbial diversity of a tropical intertidal ascidian holobiont. MARINE ENVIRONMENTAL RESEARCH, v. 194, p. 13-pg., 2023-12-26. (20/02207-5, 19/03008-9, 15/17177-6, 22/12654-4, 17/18235-5, 20/08987-2, 17/17648-4)