Coumarin MAMMEA A/BB cytotoxicity inhibits the chemoresistance and migration of glioblastoma cells in vitro

High-grade gliomas are the most aggressive brain tumors, which have no effective treatment. This work investigated a new anti-glioma strategy using mammea A/BB in vitro, a 4-phenylcoumarin isolated from the roots of Kielmeyera argentea. This work evaluated the cytotoxicity of mammea A/BB to human glioblastoma (U251), rat glioma (C6) cells and rat astrocytes in primary culture, comparing to temozolomide (TMZ) by MTT test. Cell migration assay, morphological analysis of DAPI-labeled nuclei and immunofluorescence for P-glycoprotein (P-gp) were also performed. After 72 h, the mammea A/BB significantly induced cytotoxicity in a concentration-dependent manner in U251 and C6 cells, with the EC₅₀ 27 ± 2 μM and 57 ± 14 μM, respectively. The natural compound was not cytotoxic to astrocytes in primary culture up to 200 μM. It was possible to observe a significant inhibition of tumoral cell migration in treatments with 10 mM mammea A/BB. Both cell lines were resistant to TMZ, but significantly sensitive to mammea A/BB. The percentage of picnotic nuclei of cells treated with 30 mM mammea A/BB was higher than the control. Besides, the treatment with mammea A/BB showed no significant difference in P-gp expression, but it was increased in TMZ treatment after 72 h. Even with cell lines presenting different molecular profiles, the results indicate that mammea A/BB is a promising candidate as a new antitumor drug against glioma cells in vitro.