Anti-Proliferative Effects of Evodiamine in Human Lung Cancer Cells

BACKGROUND: Evodiamine, a compound isolated from the Evodia rutaecarpa Bentham (Rutaceae), is known to have a potential anti-proliferative activity in human cancer cells. However, the growth inhibitory activity against lung cancer cells and the underlying molecular mechanisms have been poorly determined. The present study was designed to examine the anti-proliferative effect of evodiamine in A549 human lung cancer cells. METHODS: A549 cells were treated with the compounds from Evodia rutaecarpa, and the anti-proliferative activity was evaluated by the sulforhodamine B assay. The mechanisms of action for the growth inhibitory activity of evodiamine on A549 human lung cancer cells were evaluated using flow cytometry for cell cycle distribution, and Western blot for assessment of accumulation and phosphorylation of potential target proteins. RESULTS: Evodiamine exhibited a potent anti-proliferative activity against A549 human lung cancer cells. Flow cytometric analysis revealed that evodiamine induced cell cycle arrest at G2/M phase and apoptosis in the A549 cells. The cell cycle arrest was well correlated with the inhibition of cyclin B1, cyclin A, cdk2 and p-cdc2 (Tyr15) and increase of p-chk1 (Ser345) and p-chk2 (Thr68). Evodiamine also significantly increased the ratio of Bax/Bcl-2 and decreased procaspase-3, suggesting evodiamine-induced apoptosis via the intrinsic apoptotic pathway. In addition, evodiamine inhibited the expression of p-ERK and ERK. CONCLUSIONS: These findings suggest that the anti-proliferative effect of evodiamine was associated in part with the induction of G2/M phase cell cycle arrest and apoptosis, and down-regulation of ERK in human lung cancer cells.