Matteucinol combined with temozolomide inhibits glioblastoma proliferation, invasion, and progression: an in vitro, in silico, and in vivo study

ABSTRACT

Glioblastoma is the most prevalent and malignant brain tumor identified in adults. Surgical resection followed by radiotherapy and chemotherapy, mainly with temozolomide (TMZ), is the chosen treatment for this type of tumor. However, the average survival of patients is around 15 months. Novel approaches to glioblastoma treatment are greatly needed. Here, we aimed to investigate the anti-glioblastoma effect of the combination of matteucinol (Mat) (dihydroxyflavanone derived from Miconia chamissois Naudin) with the chemotherapeutic TMZ in vitro using tumor (U-251MG) and normal astrocyte (NHA) cell lines and in vivo using the chick embryo chorioallantoic membrane (CAM) assay. The combination was cytotoxic and selective for tumor cells (28 μg/mL Mat and 9.71 μg/mL TMZ). Additionally, the combination did not alter cell adhesion but caused morphological changes characteristic of apoptosis in vitro. Notably, the combination was also able to reduce tumor growth in the chick embryo model (CAM assay). The docking results showed that Mat was the best ligand to the cell death membrane receptor TNFR1 and to TNFR1/TMZ complex, suggesting that these two molecules may be working together increasing their potential. In conclusion, Mat-TMZ can be a good candidate for pharmacokinetic studies in view of clinical use for the treatment of glioblastoma.