Objective: To investigate the mechanism of shikonin-induced apoptosis in PC-3 cells. Method: The PC-3 cells were cultured and treated with different concentrations of shikonin in vitro. The anti-proliferative effect of shikonin was performed by MTT assay. The morphologic change was observed by the contrast phase microscope. Intracellular reactive oxygen species (ROS) generation was measured by flow cytometric analysis. The protein expressions of Bax

Bcl-2

Caspase-3 and p-ERK1/2 were examined by Western blot analysis. Result: Shikonin inhibited PC-3 cell growth in a time-and dose-dependent manner. The morphologic changes including cell shrinkage

cavitations

shedding and apoptosis bodies in PC-3 cells were observed after treatment with shikonin. The expressions of Bax and Caspase-3 were up-regulated

and Bcl-2 expression was down-regulated. Shikonin also induced the production of ROS in a dose-dependent manner. The cell growth inhibition ratio of shikonin-treated group was markedly decreased by ROS scavenger DTT. In addition

pretreatment of PC-3 cells with 0.2 mmol·L-1 DTT could reverse the shikonin-induced activation of Caspase-3 and ERK1/2. Conclusion: Shikonin could induce apoptosis in PC-3 cells by ROS/ERK1/2 pathways.