Preclinical study of novel tetracyclic small molecule NSC745887 for brain cancer

• Main Authors: FANN, LI-YUN, 范立筠
• Other Authors: MA, KUO-HING
• Format: Others
• Language: zh-TW
• Published: 2018
• Online Access: http://ndltd.ncl.edu.tw/handle/v2d9db

博士 === 國防醫學院 === 醫學科學研究所 === 106 === The development of a novel therapy for malignant glioma is a vigorous area in both chemistry and cancer research. Previously, we reported that the small molecule naphtho[2,3-f]quinoxaline-7,12-dione (NSC745887) effectively inhibits the proliferation of several cancers. In this study, we further investigated the therapeutic effects of NSC745887 on two human glioblastoma (GBM) cells (U118MG and U87MG) and clarified underlying mechanisms of these effects. We found that NSC745887 induced cell cycle arrest as GBM cells were accumulated in the subG1 and G2/M phases in a dose- and time-dependent manner. This effect was caused by DNA damage response in GBM cells. Moreover, the treatment of NSC745887 reduced the expression of decoy receptor 3 (DcR3) and disrupted the mitochondrial membrane signaling cascade in GBM cells, leading to apoptosis of the cells. In the heterotopic mice model, we found that the size of the GBM cell xenografts was decreased following the treatment of NSC745887, indicated by fluorine-18 fluorodeoxyglucose ([18F]-FDG) coupled with positron emission tomography (PET). These findings provide evidence from molecular, cellular, and physiological levels that strongly suggest that NSC745887 is a promising small-molecule agent for human GBM.