Effect of gedunin on glioblastoma proliferation and invasiveness:In vitroandin vivoapproaches

Abstract

AbstractGlioblastoma is the most invasive and malignant brain tumor, for which no effective treatment is currently available. Heat shock protein 90 (HSP90) is a potential target for the treatment of different types of cancer. Herein, we investigated the effect of gedunin, an HSP90 inhibitor, in murine GL261 glioblastomain vitroandin vivomodels. Gedunin treatment decreased GL261 cell proliferation and triggered apoptosis in a concentration- dependent manner. Gedunin also reduced GL261 cell migration and metalloproteinase-2 activity, suggesting that it impairs glioblastoma cell invasion. Despite the reduction of total protein content in gedunin-treated cells, the phosphorylation of STAT3 and ERK1/2 pathways was enhanced within 24 h.In situtreatment with gedunin did not significantly reduce tumor volume but reduced the presence of vascular structures in xenograft glioblastoma in C57BL/6 mice, a clinical feature associated with morbidity and mortality. Our results demonstrate that gedunin is a promising compound for the treatment of glioblastoma.Graphical AbstractHighlightsGedunin reduces GL261 cell proliferation, migration and invasionin vitro.Gedunin induces GL261 cell apoptosis and ERK activationin vitro.Gedunin reduces the presence of tumoral vascular structuresin vivo.