2-Deoxyglucose, an Inhibitor of Glycolysis, Enhances the Oncolytic Effect of Coxsackievirus

SIMPLE SUMMARY: Oncolytic viruses infect tumor cells and trigger their death and elimination by the immune system. Several viral strains have been introduced into clinical practice. However, their therapeutic efficacy remains controversial. Here, we show that Coxsackievirus B5 (CVB5) causes the death of glioblastoma cells. Interestingly, 2-deoxyglucose, an inhibitor of glycolysis augments the oncolytic effect induced by CVB5. This synergism occurs in cells with a high respiratory phenotype and increased glycolytic capacity. Thus, 2-deoxyglucose or its analogs can be evaluated further as drugs to potentiate the oncolytic effects of enteroviruses against glioblastoma multiforme. ABSTRACT: Glioblastoma multiforme (GBM) is one of the most common types of brain tumor. Despite intensive research, patients with GBM have a poor prognosis due to a very high rate of relapse and significant side effects of the treatment, with a median survival of 14.6 months. Oncolytic viruses are considered a promising strategy to eliminate GBM and other types of cancer, and several viruses have already been introduced into clinical practice. However, identification of the factors that underly the sensitivity of tumor species to oncolytic viruses or that modulate their clinical efficacy remains an important target. Here, we show that Coxsackievirus B5 (CVB5) demonstrates high oncolytic potential towards GBM primary cell species and cell lines. Moreover, 2-deoxyglucose (2DG), an inhibitor of glycolysis, potentiates the cytopathic effects of CVB5 in most of the cancer cell lines tested. The cells in which the inhibition of glycolysis enhanced oncolysis are characterized by high mitochondrial respiratory activity and glycolytic capacity, as determined by Seahorse analysis. Thus, 2-deoxyglucose and other analogs should be considered as adjuvants for oncolytic therapy of glioblastoma multiforme.