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• W3135763411 endingPage "173975" @default.
• W3135763411 startingPage "173975" @default.
• W3135763411 abstract "Natural products are a large source of clinically effective antitumor drugs. Millepachine, a natural product derived from leguminous plants, was reported to display antitumor activity. In this study, the novel compound, (1H-indol-5-yl) (5-methoxy-2,2-dimethyl-2H-chromen-8-yl)methanone (MIL-1), was designed and synthesized by fusing millepachine and indole rings. MIL-1 exerted much better antitumor activity than millepachine, manifesting as a 24- to 201-fold increase in vitro cytotoxicity and a 2.4-fold increase in in vivo antitumor activity in hepatocellular cell lines-derived models. The immunofluorescence and HPLC detection revealed that MIL-1 was a potent microtubule targeting agent by interfering with the equilibrium of tubulin-microtubule dynamics and irreversibly binding to tubulin. MIL-1 displayed remarkable antitumor activity with an IC50 of 31–207 nM towards various human cancer cell lines derived from various organs and tissues, and it exerted no evidence of toxicity against normal cells. Mechanistic studies showed that MIL-1 arrested the cell cycle at G2/M phase and induced apoptosis by activating caspase-3 activity and reactive oxygen species (ROS) accumulation. Moreover, the superior antitumor effect of MIL-1 is worthy of further detailed study for the treatment of hepatocellular carcinoma (HCC)." @default.
• W3135763411 created "2021-03-15" @default.
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• W3135763411 date "2021-05-01" @default.
• W3135763411 modified "2023-10-16" @default.
• W3135763411 title "MIL-1, a novel antitumor agent derived from natural product millepachine, acts as tubulin polymerization inhibitor for the treatment of hepatocellular carcinoma" @default.
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• W3135763411 doi "https://doi.org/10.1016/j.ejphar.2021.173975" @default.
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