The bacterial protein toxin, cytotoxic necrotizing factor 1 (CNF1) provides long-term survival in a murine glioma model

摘要: Glioblastomas are largely unresponsive to all available treatments and there is therefore an urgent need for novel therapeutics. Here we have probed the antineoplastic effects of a bacterial protein toxin, cytotoxic necrotizing factor 1 (CNF1), in syngenic GL261 glioma cell model. CNF1 produces long-lasting activation Rho GTPases, with consequent blockade cytodieresis proliferating cells promotion neuron health plasticity. We tested antiproliferative on human obtained from surgical specimens. For vivo experiments, injected into adult mouse visual cortex, five days later administered either single intracerebral dose or vehicle. To compare canonical antitumoral drug, infused temozolomide (TMZ) via minipumps 1 week additional animal group. In culture, was very effective blocking proliferation cells, leading them multinucleation, senescence death within 15 days. had similar effect primary cells. also inhibited motility scratch-wound migration assay. Low (2 nM) continuous TMZ infusion significantly prolonged survival (median 35 days vs. 28 days vehicle controls). Remarkably, increasing concentration 80 nM resulted dramatic enhancement no obvious toxicity. Indeed, 57% CNF1-treated animals survived up 60 days following transplant. The GTPases by represents potential therapeutic strategy treatment central nervous system tumors.