Mechanisms of tanshinone IIA in the Helicobacter pylori-infected MKN45 cell apoptosis

• Main Authors: Yu-Chieh Shu, 許喻捷
• Other Authors: Yuan-Chuen Wang
• Format: Others
• Language: zh-TW
• Published: 2014
• Online Access: http://ndltd.ncl.edu.tw/handle/65441606392151351488

碩士 === 國立中興大學 === 食品暨應用生物科技學系所 === 102 === Helicobacter pylori is strongly associated with chronic gastritis, peptic ulcer, and gastric cancer. Chronic gastritis plays an important role in the progression of gastric cancer. Apoptosis is a key factor to inhibit gastric cancer progression. World Health Organization (WHO) defined H. pylori as a group I carcinogen in 1994. Tanshinone IIA, an diterpene quinones, was isolated from the roots of Salvia miltiorrhiza, having anti-inflammatory and anti-cancer activities. In our previous study, tanshinone IIA exhibited anti-inflammatory effect in the H. pylori-infected MKN45 cell. Therefore, in this study, the effects of tanshinone IIA on the H. pylori-infected gastric adenocarcinoma MKN45 cell apoptosis were investigated. Tanshinone IIA treatment (16 μg/mL) significantly inhibited MAPK pathway (p38 and JNK1/2) and 5-LOX protein expressions; 70, 67, and 65% of that of the controls (0 μg/mL treatment), respectively. Tanshinone IIA treatment (16 μg/mL) significantly increased subG0/G1 phase of the cell cycle, 246% of that of the control. The mitochondrial membrane potential significantly collapsed, 71% of that of the control at 16 μg/mL of treatment dose. Tanshinone IIA (16 μg/mL) significantly increased Bax, cytosolic cytochrome c, and caspase-9 protein expressions; 292, 200 and 173% of that of controls, respectively. Tanshinone IIA (16 μg/mL) significantly decreased Bcl-2, mitochondrial cytochrome c, and pro-caspase-3 protein expressions; 55, 56, and 36% of that of controls, respectively. Tanshinone IIA significantly inhibited MAPK pathway’s protein expressions resulted in the inhibition of downstream inflammatory factors, and then H. pylori-infected cell inflammation was significantly inhibited. Inflammatory factor inhibition was responsible for the activation of pro-apoptotic protein (Bax). Tanshinone IIA significantly inhibited Bcl-2 and increased Bax protein expressions, and then induced mitochondrial membrane potential collapsed. Subsequently, cytochrome c was released from mitochondria to cytosol resulted in the activation of caspase-9 and pro-caspase-3, and then triggered MKN45 cell apoptosis. In conclusion, tanshinone IIA significantly inhibited inflammatory signaling transduction and induced apoptosis in the H. pylori-infected MKN45 cells. Tanshinone IIA showed great potential to prevent gastric cancer progression in the H. pylori-infected cells.