MSACL 2019 EU Abstract

Prostate Cancer Metabolic Alterations Induced by Zika Virus

Jeany Delafiori (1), Estela de Oliveira Lima (2), Mohamed Ziad Dabaja (1), Flávia Luísa Dias-Audibert (1), Diogo Noin de Oliveira (1), Carlos Fernando Odir Rodrigues Melo (1), Karen Noda Morishita (1), Geovana Manzan Sales (1), Ana Lucia Tasca Gois Ruiz (3), Gisele Goulart (3), Marcelo Lancellotti (4), and Rodrigo Ramos Catharino (1)
(1) Innovare Biomarkers Laboratory, Faculty of Pharmaceutical Sciences, University of Campinas (UNICAMP), Campinas, São Paulo, Brazil (2) Medical School, São Paulo State University (UNESP), Botucatu, São Paulo, Brazil (3) Faculty of Pharmaceutical Sciences, University of Campinas (UNICAMP), Campinas, São Paulo, Brazil (4) Laboratory of Biotechnology, Faculty of Pharmaceutical Sciences, University of Campinas (UNICAMP), Campinas, São Paulo, Brazil

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Jeany Delafiori (Presenter) University of Campinas >> POSTER (PDF)

Presenter Bio: I am Jeany Delafiori, PhD student at University of Campinas (UNICAMP) supervised by Prof. Dr. Rodrigo Ramos Catharino. I am currently studying Zika virus activity on cancer cells as my PhD thesis and participating in projects related to the clinical application of mass spectrometry for the identification of biomarkers and metabolic alterations in diseases.

Relevant Financial Disclosures (within past 24 months) No relevant financial relationship(s) to disclose. Conflict mitigation NOT REQUIRED.

Introduction: Zika virus (ZIKV) is a flavivirus transmitted by Aedes aegypti mosquito, with high incidence of cases on Americas between 2015 and 2016. Although 80% of the cases are asymptomatic, ZIKV infection was associated to neurological complications such as Guillain-Barré syndrome and microcephaly. Based on these reports several initiatives started to understand viral infection process in human and mosquito cells. During experimental investigations it was demonstrated that ZIKV can impair neuronal growth, reduce neural stem cell and even mediate cell death. A hypothesis about the oncolytic potential of ZIKV due its ability of cell growth impairment was raised and later confirmed by in vitro and in vivo studies with glioblastoma cells. The antiproliferative effect of a ZIKV prototype (ZVp) was tested for several types of tumor cell resulting in ZVp activity against prostate cancer cells (PC-3). However, little is known about the cellular mechanisms associated prostate cancer cell death induced by Zika moieties.
Objective: Determine prostate cancer cell line (PC-3) metabolic alterations induced by Zika virus particle using high resolution mass spectrometry (HRMS).
Methods: A PC-3 cell in vitro model was exposed to ZVp for 24 hours and a group of non-exposed cells was used as control. Cells and supernatant were collected and the metabolites were extracted, ionized and directly injected in a HRMS instrument, ESI-LTQ-XL Orbitrap Discovery (Thermo Scientific, Bremen, Germany). The analysis was performed at the mass range of 400-1200 m/z in the negative and positive ion mode. The spectral data was analyzed using a Partial Least Squares Discriminant Analysis (PLS-DA). A VIP score list (Variable Importance in Projection) from MetaboAnalyst 4.0 software was used to determine the characteristic ions for ZVp exposed group. Using online databases potential biomarkers were identified (error <2ppm) and confirmed by tandem MS experiments.
Results: PLS-DA showed a marked separation between PC-3 exposed and non-exposed groups, suggesting discriminant molecules involved ZIKV induced cell alterations. The 20 proposed chemical markers translate lipid metabolism remodeling associated with ZIKV interaction with cell, inflammatory mediators and inductors of cell death. In addition, based on markers we proposed the involvement of one carbon metabolism, porphyrin pathway and protein glycosylation on ZIKV antiproliferative effect. The versatility of the metabolomic screening helped to indicate pathways that may be involved with ZIKV antiproliferative effect and are not so obvious for a first target study.
Conclusion: To our knowledge this is the first metabolomic investigation of ZIKV interaction with prostate cancer cells. Metabolomic strategies associated with HRMS have been supporting advances in ZIKV research, bringing innovation to viral infection biomarkers elucidation, developing diagnostic methods and understanding of ZIKV mechanisms and oncolytic potential.