MALDI imaging detects endogenous digoxin in glioblastoma cells infected by Zika virus: would it be the oncolytic key?

Autor(es): Lima, Estela de O.; Guerreiro, Tatiane M.; Melo, Carlos Fernando O.R.; Oliveira, Diogo N. de; Machado, Daisy; Lancelloti, Marcelo; Catharino, Rodrigo R.

Resumo: Recently, microcephaly cases have increased in Americas and have been matter of concern due to Zika virus (ZIKV) recent outbreak. Previous studies have shown that ZIKV-infected progenitor neuronal cells present morphological abnormalities and increased rates of cell death, which may be indicators of microcephaly causes. As recent studies indicate ZIKV' tropism for brain cells, how would a glioblastoma (GBM) lineage behave under ZIKV infection, considering GBM the most common and malignant brain tumor in adults, presenting extreme chemoresistance and high morbidity and mortality rates? The current trend of using genetically engineered oncolytic pathogens as a safe way to eliminate tumors is under development, with trials already in course. Therefore, the present study evaluated the possible oncolytic effects and metabolomic alterations of ZIKV infection at human malignant M059J GBM cells. Microscopic evaluation was performed by using optical microscopy, which showed cytopathic effects induced by ZIKV at GBM cells. For the metabolomics study, both control and infected cell cultures were submitted to matrix laser desorption/ionization mass spectrometry imaging analysis. Mass spectrometry data were submitted to partial least squares discriminant analysis statistical analysis, and distinct biomarkers were elected for each infected groups. This study brings light to unexpectedly induced metabolic changes, as endogenous digoxin as important biomarker for ZIKV-GBM group, associated with cytopathic effects induced by viral infection. These result evidences that genetically engineered ZIKV might be a potential new strategy for neural cancer management through the induction of endogenous digoxin synthesis in GBM cells.

Palavras-Chave: Digoxin; MALDI imaging; Mass spectrometry; Metabolomics; Zika virus

Imprenta: Journal of Mass Spectrometry, v. 53, n. 3, p. 257-263, 2018

Identificador do objeto digital: 10.1002/jms.4058

Descritores: Zika virus - Molecular Structure

Data de publicação: 2018