Extracts of Cerbera manghas L. effectively inhibit the viability of glioblastoma cell lines and their cancer stemloids in vitro and in mouse xenograft model

Glioblastoma multiforme (GBM), a highly recurrent malignant disease, is a grade IV glioma with poor prognosis. Glioblastoma stem cells (GSCs) are the new potential target for GBM intervention. To develop an improved treatment by targeting GSCs, we identified neriifolin, an active principle in extracts of Cerbera manghas L., as an effective inhibitor for the growth and migration of GBM cell lines and their tumorspheres. In this study, neriifolin effectively inhibited the growth and colony formation of CD133⁺ GBM tumorspheres. Both C. manghas extracts and neriifolin inhibited Akt activation and caused cell cycle G1 arrest. They also reduced the expression of the stem cell marker Sox2. Treatment with their higher doses induced the apoptosis of GBM tumorspheres. Furthermore, neriifolin inhibited the growth of CD133⁺ GBM tumorsphere-derived tumors in vivo. In summary, neriifolin obtained from extracts of C. manghas may serve as a drug lead compound for GBM therapies.