Isolated Components From Spider Venom Targeting Human Glioblastoma Cells and Its Potential Combined Therapy With Rapamycin.

Autor:	Caballero M; Faculdade de Ciências Farmacêuticas, Universidade Estadual de Campinas (UNICAMP), Campinas, Brazil.; Departamento de Biologia Estrutural e Funcional, Instituto de Biologia, UNICAMP, Campinas, Brazil., Barreto N; Faculdade de Ciências Farmacêuticas, Universidade Estadual de Campinas (UNICAMP), Campinas, Brazil.; Departamento de Biologia Estrutural e Funcional, Instituto de Biologia, UNICAMP, Campinas, Brazil., Bonfanti AP; Faculdade de Ciências Farmacêuticas, Universidade Estadual de Campinas (UNICAMP), Campinas, Brazil.; Departamento de Biologia Estrutural e Funcional, Instituto de Biologia, UNICAMP, Campinas, Brazil., Munhoz J; Faculdade de Ciências Farmacêuticas, Universidade Estadual de Campinas (UNICAMP), Campinas, Brazil.; Departamento de Biologia Estrutural e Funcional, Instituto de Biologia, UNICAMP, Campinas, Brazil., Rocha E Silva T; Faculdade Israelita de Ciências da Saúde Albert Einstein, São Paulo, Brazil., Sutti R; Faculdade de Ciências Médicas, Santa Casa de São Paulo, São Paulo, Brazil., Verinaud L; Departamento de Biologia Estrutural e Funcional, Instituto de Biologia, UNICAMP, Campinas, Brazil., Pinheiro de Mato FC; Faculdade de Ciências Farmacêuticas, Universidade Estadual de Campinas (UNICAMP), Campinas, Brazil.; Departamento de Biologia Estrutural e Funcional, Instituto de Biologia, UNICAMP, Campinas, Brazil., Lanfredi GP; Departamento de Bioquímica e Imunologia, Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo (FMRP-USP), São Paulo, Brazil., Rapôso C; Faculdade de Ciências Farmacêuticas, Universidade Estadual de Campinas (UNICAMP), Campinas, Brazil.
Jazyk:	angličtina
Zdroj:	Frontiers in molecular biosciences [Front Mol Biosci] 2022 Mar 14; Vol. 9, pp. 752668. Date of Electronic Publication: 2022 Mar 14 (Print Publication: 2022).
DOI:	10.3389/fmolb.2022.752668
Abstrakt:	Glioblastomas (GBs) are responsible for a higher mortality rate among gliomas, corresponding to more than 50% of them and representing a challenge in terms of therapy and prognosis. Peptide-based antineoplastic therapy is a vast and promising field, and these molecules are one of the main classes present in spider venoms. Recently, our research group demonstrated the cytotoxic effects of Phoneutria nigriventer spider venom (PnV) in GBs. The present study aimed to select the purified PnV-components with potential antineoplastic effects, as well as to compare different metabolic conditions. Human GB (NG97) cells were treated with the PnV fractions: F1 (less than 3 kDa), F2 (between 3 and 10 kDa), and F3 (greater than 10 kDa). After treatments, viability (MTT), proliferation (CFSE), death (Annexin V/propidium iodide-PI), and cell cycle (PI) assays were performed. The F1 and F2 fractions in acute periods (1 and 5 h) and low concentrations (0.1 and 1 μg/ml) showed more relevant effects and were repurified in subfractions (SF1-SF11); from these, SF3 and SF4 showed the most significant effects. The previous inhibition of mTOR by rapamycin had a synergistic effect with SFs, reducing cell viability even more significantly than the untreated control. Taken together, the results point to components present in SF3 and SF4 as potential prototypes for the development of new drugs for GB treatment and stimulate studies to use these compounds in combination therapy with a rapamycin-like activity. Future studies will be conducted to characterize, synthesize the molecules, and to evaluate the efficacy and safety in preclinical models. Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. (Copyright © 2022 Caballero, Barreto, Bonfanti, Munhoz, Rocha e Silva, Sutti, Verinaud, Pinheiro de Mato, Lanfredi and Rapôso.)
Databáze:	MEDLINE
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