Metabolic alterations induced by attenuated Zika virus in glioblastoma cells

Author(s):Show less -

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]

Affiliation

^[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

• Document type: Journal article
• Source: CELL AND BIOSCIENCE; v. 8, SEP 4 2018.
• Web of Science Citations: 1

Abstract

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)

• FAPESP's process: 15/06809-1 - Determination of chemical markers in various bovine products using mass spectrometry
• Grantee: Rodrigo Ramos Catharino
• Support Opportunities: Regular Research Grants
• FAPESP's process: 11/50400-0 - Mitochondrial energy metabolism, redox state and functionality in cell death and cardiometabolic and neurodegenerative disorders
• Grantee: Aníbal Eugênio Vercesi
• Support Opportunities: Research Projects - Thematic Grants
• FAPESP's process: 16/17066-2 - Metabolomics and lipidomics the Zika virus, from mosquitoes to the patient
• Grantee: Carlos Fernando Odir Rodrigues Melo
• Support Opportunities: Scholarships in Brazil - Doctorate
• FAPESP's process: 13/07607-8 - OCRC - Obesity and Comorbidities Research Center
• Grantee: Licio Augusto Velloso
• Support Opportunities: Research Grants - Research, Innovation and Dissemination Centers - RIDC