Abstract
Abstract Glioma is a severe disease with poor prognosis. Chemotherapy plays an important role but very few drugs are effective. There are two major issues: (1) the specialized blood-brain barrier blocks most large molecules from penetrating into target area; (2) tumor cells frequently develop drug resistant. Therefore, developing new chemotherapeutic agents for malignant brain tumor treatment may significantly improve the current difficulties. Compounds derived from nature products have been considered as potential sources for new discovery of anti-cancer drug. Manzamine A-derived compounds, showed significant anticancer activities against colon adenocarcinoma DLD cells, lung large cell carcinoma NCI-H661 cells, and hepatoma HepG2/A2 cells. In this study, we used in vitro model for screening these compounds and discovered both cytotoxic and anti-proliferative effects against brain tumor cells, such as A172, U87MG, and GL261 cell lines. We then used animal models to test the toxicities and treatment effect of compound A3 in vivo, and delivered the agent by convection-enhanced delivery to improve drug concentration in brain. Survival benefit for brain tumor-bearing animal was found for optimal dosage of compound A3. Details of anti-tumor mechanism need further evaluation.
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