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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 cycle arrest was ascribed to the down-regulation of cyclin B and cyclin dependent kinase 1, while the enhanced induction of apoptosis was due to the activation of caspase -3, -8 and -9 and the decreased B-cell lymphoma 2/ assaciated X protein ratio. Furthermore, the in vivo kinetic, bioavailability and in situ absorption characteristics of EVONE were much better than those of free evodiamine. The cancer cells insensitive to free chemodrugs became sensitive to nanoemulsive chemodrugs.

Efficient intracellular delivery makes cancer cells sensitive to nanoemulsive chemodrugs