Tanshinone Ⅱ A (Tan Ⅱ A) is a monomer isolated from Salvia miltiorrhiza Bunge (Danshen) with anti-cancer effects recently reported for a variety of cancer cell types in vitro.However, the effects of Tan Ⅱ A on esophageal carcinoma cell lines are still unknown.In the present study,we evaluated the effects of Tan Ⅱ A on two esophageal carcinoma cell lines (EC-1 cells and ECa-109) and explored its mechanism.The CCK-8 and colony formation assay indicated that Tan Ⅱ A inhibited the cell proliferation of human esophageal cancer cells (IC50below 1 μg/ml) at 48h.Hoechst 33258 and flow cytometry showed that Tan Ⅱ A induced apoptosis in both esophageal cancer cell lines.After treatment with 1.3μg/ml Tan Ⅱ A for 48h,the apoptosis index increased from (5.68±0.42)% to (40.21±2.64) % in EC-1 cells and from (5.08±1.06)% to (60.62±3.81)% in ECa-109 cells.A cell cycle assay indicated that treatment of EC-1 and ECa-109 cells with 1.3 μg/mL Tan Ⅱ A for 48h increased the percentage of cells in S phase[(46.44±2.26)% and (40.84±6.41)%, vs.control (28.55±0.34)% and (33.89±1.98)%] and G2/M phase [(14.11 ±1.56)% and (15.16±3.44)%, vs.control (9.51±2.03)% and (8.99±1.62)%].Western blot analysis showed that Aktl and its phosphorylation were inhibited,the Bax/Bcl-2 ratio increased,and both caspase9 and caspase3 were activated after treatment with 1.3 μg/ml Tan Ⅱ A at 48h.Meanwhile, p53 and p21 protein levels increased, whereas, cyclin B1, Cdc2, and Cdc2 phosphorylation were inhibited.These results show that Tan Ⅱ A inhibits the growth of esophageal cancer cells and induces apoptosis in a time-dependent and concentration-dependent manner.Tan Ⅱ A can also induce changes in the cell cycle,increasing the percentage of cells in S and G2/M phase.These results show that Tan Ⅱ A may be a new candidate for the treatment of esophageal cancer.