Glioblastoma multiforme (GBM) is the grade IV glioma and the most common adult primary brain tumor. It is notorious for its heterogeneity, invasiveness and resistance to chemo- and radiotherapies. These characteristics make it a highly recurrent malignant disease with poor prognosis. The potential new target for intervention in GBM is its cancer stem cells (GSCs).
To identify an improved treatment by targeting GSCs, we screened 400 botanical extracts for their effects on cytotoxicity and colony formation ability in GBM cell lines and tumorspheres.
We identified the extracts of Cerbera manghas L. as being effective inhibitors of the growth and migration of GBM cell lines and its tumorspheres. We further demonstrated that neriifolin was one of the active principles. Neriifolin effectively inhibits the growth of CD133+-GBM tumorspheres and their colony formation. The extracts of Cerbera and neriifolin both reduced AKT activation and caused cell cycle G1 arrest while reducing the protein level of the stem cell marker Sox2. Furthermore, higher doses of these treatments induced apoptosis of tumorspheres. In the mouse xenotransplantation model, 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.
Clinical trial identification
Legal entity responsible for the study
Department of life Science, National Taiwan Normal University.
Ministry of Science and Technology, Taiwan, ROC.
Louise T. Chow.
All authors have declared no conflicts of interest.