DMXAA-pyranoxanthone hybrids enhance inhibition activities against human cancer cells with multi-target functions

摘要

Abstract Four 5,6-dimethylxanthone-4-acetic acid ( D ) and pyranoxanthone ( P ) hybrids ( D-P-n ) were design-synthesized based on multi-target-addressed strategy. D-P-4 was confirmed as the most active agent against HepG-2?cell line growth with an IC 50 of 0.216?±?0.031?μM. Apoptosis analysis indicated different contributions of early/late apoptosis/necrosis to cell death for both monomers, the combination ( D ?+? P in 1:1?mol ratio) and D-P-4 . They all arrested more cells on S phase. Western Blot implied that D-P-4 regulated p53/MDM2 to a better healthy state. Moreover, it improved Bax/Bcl-2 signaling pathway to increase cancer cell apoptosis. In all cases studied, D-P-4 showed the best activity and synergistic effect. All the evidences support that D-P-4 is a better anti-cancer therapy with multi-target functions. Graphical abstract Display Omitted Highlights ? D-P-4 hybrid increased the activity against the growth of HepG-2 cancer cells by 460 times compared to DMXAA. ? D-P-4 regulated p53/MDM2 to a better healthy state than both monomers and the combination. ? D-P-4 showed better activity in regulating Bax/Bcl-2 to increase HepG-2?cell apoptosis. ? D-P-4 arrested more cells on S phase compared with any one of the two monomers or the combination.