Ailanthone up-regulates miR-449a to restrain acute myeloid leukemia cells growth, migration and invasion.

Ailanthone (AIL) is a quassinoid isolated from traditional Chinese herbal medicine Ailanthus altissima. The anti-tumor activities of AIL have been reported in various solid tumors. This study aimed to reveal the in vitro effect of AIL on acute myeloid leukemia (AML) cells.The effects of AIL on five AML cell lines (KG1, HL60, U-937, THP-1 and OCI-AML2) as well as myeloid progenitor cells were evaluated by performing CCK-8 assay, flow cytometry, Transwell assay and Western blotting. KG1 and HL60 cells were transfected with miR-449a inhibitor or its negative control, and then were treated by AIL. The above mentioned assays were performed again to study the involvement of miR-449a in AIL's function.AIL dose-dependently inhibited the viability of AML cells and myeloid progenitor cells. The IC50 value of AIL towards KG1 and HL60 cells was 0.58 and 0.57 μM, respectively. AIL with concentration of 0.5 μM significantly induced the apoptosis of AML cells rather than myeloid progenitor cells. Meanwhile, 0.5 μM AIL significantly reduced migration and invasion of AML cells. miR-449a was highly expressed in response to the treatment of 0.5 μM AIL. Besides this, the anti-tumor activities of AIL in AML cells were attenuated by miR-449a silence. Further, the blockage of Notch and PI3K/AKT signaling pathways induced by AIL was reversed by miR-449a silence.AIL restrained AML cells growth, migration and invasion through up-regulation of miR-449a, and deactivation of Notch and PI3K/AKT signaling pathways.