Tanshinone IIA inhibits gastric carcinoma AGS cells through increasing p-p38, p-JNK and p53 but reducing p-ERK, CDC2 and cyclin B1 expression.

Tanshinone IIA (Tan-IIA) is extracted from Danshen (Salviae miltiorrhizae radix). It possesses antitumor activity against a variety of human cancer cells and its induction of apoptosis and inhibition of proliferation of gastric cancer cells are well-documented. However, the molecular mechanisms by which Tan-IIA inhibits gastric cancer have not been well-elucidated. In the present study, we evaluated the cytotoxicity of Tan-IIA against human gastric cancer AGS cells by the (3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide) MTT assay. The protein expression of tumor necrosis factor-alpha (TNF-α), FAS, p53, p21, cyclin A, cyclin B1, extracellular-related kinase (ERK), phospho extracellular-related kinase (p-ERK), p38, p-p38, Jun-amino-terminal kinase (JNK), phospho Jun-amino-terminal kinase (p-JNK) and β-actin in AGS cells were measured by western blotting. The cell-cycle distribution was analyzed by flow cytometry. The results showed that Tan-IIA inhibited AGS cells with time- and dose-dependent manners. AGS cells treated with Tan-IIA up-regulated the protein expression of TNFα, FAS, p-p38, p-JNK, p53, p21, caspase-3 and caspase-8 but reduced that of p-ERK, CDC2, cyclin A, and cyclin B1. The results also showed that Tan-IIA dose dependently induced G2/M phase arrest. These findings demonstrate that Tan-IIA can inhibit AGS human gastric cancer cells; one of the molecular mechanisms may be through increasing the protein expression of p-p38 and p-JNK, but decreasing that of p-ERK to induce the activation of p53, followed by increasing the protein expression of p21 to down-regulate CDC2 and cyclin B1 expression which then induces G2/M phase arrest. Another route may be through increasing the protein expression of TNF-α, FAS, caspase-8 and caspase-3 to induce apoptosis.

Su CC 《-》

Tanshinone IIA inhibits human gastric carcinoma AGS cell growth by decreasing BiP, TCTP, Mcl‑1 and Bcl‑xL and increasing Bax and CHOP protein expression.

Su CC 《-》

Tanshinone IIA inhibits BT-20 human breast cancer cell proliferation through increasing caspase 12, GADD153 and phospho-p38 protein expression.

Yan MY ，Chien SY ，Kuo SJ ，Chen DR ，Su CC ... -  《-》

A monomer purified from Paris polyphylla (PP-22) triggers S and G2/M phase arrest and apoptosis in human tongue squamous cell carcinoma SCC-15 by activating the p38/cdc25/cdc2 and caspase 8/caspase 3 pathways.

Ke JY ，Zhang W ，Gong RS ，Cen WJ ，Huang HQ ，Li YR ，Kong WD ，Jiang JW ... -  《-》

Tanshinone IIA inhibits gastric carcinoma AGS cells by decreasing the protein expression of VEGFR and blocking Ras/Raf/MEK/ERK pathway.

Su CC 《-》