Background : Gliomas and glioblastomas are space-occupying brain tumors with variable aggressive behaviour. Glioblastomas are the most lethal brain tumors and are not responsive to current chemotherapy and radiotherapy. To date, no satisfactory curative treatment exists. 3-bromopyruvate (3BP) is a promising chemotherapeutic that proved effective in treating gliomas and other malignancies in so many reported studies. 3BP is both an alkylating agent and antimetabolite (pharmacological antagonist of lactate, the Warburg effect). Our previous publications proved effectiveness of 3BP in treating glioma cell lines (2D models) and early glioma spheroids (3D models) where 3BP was added early after culturing glioma cells. No report is there regarding treating well-established glioma spheroids (well-established avascular 3D tumor models) using 3BP that we report here. In this study, our data revealed that
3BP effectively and maximally killed cultured glioma cells causing cellular fragmentation that correlated with maximal glioma cell death. However, the picture was less promising when treating well-established 3D glioma spheroids with 3BP where glioma viability and size decreased significantly (in a dose-dependent manner) but not maximally. There was no significant difference in spheroids cell killing at high versus very high doses of 3BP. 3BP may face many problems regarding delivery and targeting to glioma cells inside spheroid body. A similar effect may be faced when treating clinical tumors with 3BP. 3BP formulations inside lipid nanocarriers (liposomes), PEGylated liposomes or targeted liposomes may improve 3BP-induced tumor cells killing. More future research is needed to explore the reasons why 3BP effects in cell lines were not effectively translated into 3D models and how to
overcome the obstacles.