Effects of baicalein on proliferation, apoptosis, migration and invasion of Ewing's sarcoma cells

Ewing's sarcoma (ES) is a rare tumor that is more frequent in pediatric and adolescent age groups. In the past few decades, long-term survival in affected patients has improved due to the success of multimodal therapy. However, long-term survival is inevitably restricted by the late side-effects of chemotherapy. Besides, early metastasis also contributes to the poor prognosis of ES. Recently, traditional Chinese medicines (TCMs) have increasingly attracted interest due to the promising clinical results and fewer side-effects for the treatment of cancers. Among the various TCMs, the root of Scutellaria baicalensis exerts anti-inflammatory properties as a well-known herb in traditional Chinese medicine. Baicalein (5,6,7-trihydroxyflavone) derived from the root of Scutellaria baicalensis is a bioactive compound, which possesses a powerful pro-apoptotic activity in various cancers such as hepatocellular carcinoma and myeloma. However, the effects of baicalein on ES cells remain still unknown. We anticipated that baicalein also has apoptotic activity in ES. The aim of the present study was to investigate the effects of baicalein on viability, apoptosis, migration and invasion of ES cells, and further to elaborate the molecular mechanism of baicalein-induced ES cell apoptosis. We found that baicalein markedly inhibited ES cells viability in a time- and dose-dependent manner, especially SK-ES-1 cells and could promote the apoptosis of ES cells. Additionally, baicalein was capable of upregulating the expression of the pro-apoptotic proteins Bax and cytochrome c, reducing the expression of the anti-apoptotic protein Bcl-2, elevating the ratio of Bax/Bcl-2, and triggering the mitochondrial apoptotic pathway, which led to caspase-3 and caspase-9 activation and PARP cleavage. Meanwhile, the activation of caspase-8 and the death receptor pathway was also observed. Besides, baicalein could reduce ES migration and invasion in vitro, which showed its potential to inhibit ES metastasis, besides contributing to the decrease in the expression of matrix metalloproteinases (MMP)-2 and MMP-9. In conclusion, baicalein has a potent tumor-suppressor activity by inducing cell apoptosis through the mitochondrial apoptotic pathway and the death receptor pathway in ES cells, thus it may serve as a novel and effective candidate agent for ES treatment.