Metabolic alterations induced by attenuated Zika virus in glioblastoma cells

Autor(es):Mostrar menos -

Dabaja, Mohamed Ziad ^[1] ; Lima, Estela de Oliveira ^[1] ; de Oliveira, Diogo Noin ^[1] ; Guerreiro, Tatiane Melina ^[1] ; Odir Rodrigues Melo, Carlos Fernando ^[1] ; Morishita, Karen Noda ^[1] ; Lancellotti, Marcelo ^[2] ; Tasca Gois Ruiz, Ana Lucia ^[3] ; Goulart, Gisele ^[3] ; Duarte, Diego Andreazzi ^[4] ; Catharino, Rodrigo Ramos ^[1]

Afiliação do(s) autor(es)

^[1] Univ Estadual Campinas, UNICAMP, Sch Pharmaceut Sci, Innovare Biomarkers Lab, Campinas, SP - Brazil

^[2] Univ Estadual Campinas, UNICAMP, Sch Pharmaceut Sci, Lab Biotechnol, Campinas, SP - Brazil

^[3] Univ Estadual Campinas, UNICAMP, Fac Pharmaceut Sci, BR-13081970 Campinas, SP - Brazil

^[4] Univ Estadual Campinas, UNICAMP, Fac Med Sci, Renal Pathophysiol Lab, Campinas, SP - Brazil

• Tipo de documento: Artigo Científico
• Fonte: CELL AND BIOSCIENCE; v. 8, SEP 4 2018.
• Citações Web of Science: 1

Resumo

Background: Zika virus (ZIKV) has recently become a major matter of concern since its association with microcephaly cases in newborns was determined. From then on, ZIKV has been untiringly studied, and several scientific data have shown the virus' tropism to neural cells. Previous studies have proposed that ZIKV induced glioblastoma cells death, suggesting that ZIKV and ZIKV-associated molecules might induce intracellular biochemical alterations, and thereby be alternatives for neural cancer management. In this sense, the present contribution presents a prospective approach for glioblastomas management: producing a ZIKV-based therapy that stimulates glioblastoma control. We developed an attenuated ZIKV prototype based on bacterial outer membrane vesicles (OMV). The attenuated ZIKV was applied on glioblastoma cells, where cytopathic and cytostatic effects were evaluated. Glioblastoma cells, with and without treatment, were submitted to mass spectrometry analysis. Results: Microscopic analysis showed cytopathic effects induced by ZIKV prototype on glioblastoma cells after 24 and 48 h post-treatment. DNA fragmentation assay and TNF-alpha expression were indicative that ZVp induced cell damage and death. The metabolomics investigation elected 5 different biomarkers that might be associated with cell cytopathic effects, highlighting intracellular biochemical modifications induced by the attenuated ZIKV. The remarkable evidence of cell death in glioblastoma stimulated further studies that rendered a preliminary screening with other tumor cell lineages, though anti-proliferative activity test. Among the 11 tumors evaluated, prostate and ovarian tumors were the most affected by ZIKV prototype, and other 6 cell lines also presented cytostatic effects. Conclusions: Results ultimately demonstrated that this prototype not only emerges as a potential alternative for glioblastoma management, but may also be an important tool against other important tumors. (AU)

• Processo FAPESP: 15/06809-1 - Determinação de marcadores químicos em diferentes produtos bovinos por Espectrometria de Massas
• Beneficiário: Rodrigo Ramos Catharino
• Modalidade de apoio: Auxílio à Pesquisa - Regular
• Processo FAPESP: 11/50400-0 - Metabolismo energético, estado redox e funcionalidade mitocondrial na morte celular e em desordens cardiometabólicas e neurodegenerativas
• Beneficiário: Aníbal Eugênio Vercesi
• Modalidade de apoio: Auxílio à Pesquisa - Temático
• Processo FAPESP: 16/17066-2 - Metabolômica e lipidômica do Zika vírus, do mosquito ao paciente
• Beneficiário: Carlos Fernando Odir Rodrigues Melo
• Modalidade de apoio: Bolsas no Brasil - Doutorado
• Processo FAPESP: 13/07607-8 - CMPO - Centro Multidisciplinar de Pesquisa em Obesidade e Doenças Associadas
• Beneficiário: Licio Augusto Velloso
• Modalidade de apoio: Auxílio à Pesquisa - Centros de Pesquisa, Inovação e Difusão - CEPIDs