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Evodiamine has been documented to possess activities in numerous cancer cells. Our preliminary study showed that A549 cells were insensitive to evodiamine. In this paper, A549 cells are sensitive to nanoemulsive evodiamine (EVONE) through an efficient intracellular and systematic delivery. EVONE entered tumor cells by energy-dependent and mainly through clathrin-mediated endocytosis. EVONE exerted a higher cytotoxicity in a dose-and time-dependent manner. The enhanced induction of cell cycledoi:10.18632/oncotarget.17536 pmid:29029410 pmcid:PMC5630310 fatcat:7e4xsxhkuza4nhn74lb5zofzvq