Temporal Phosphoproteome Dynamics Reveal Response Pathways of Tanshinone IIA in Gastric Cancer AGS Cells

• Main Authors: Shih Chieh Kao, 高士傑
• Other Authors: Hsueh-Fen Juan
• Format: Others
• Language: en_US
• Published: 2015
• Online Access: http://ndltd.ncl.edu.tw/handle/27600146892198224896

碩士 === 國立臺灣大學 === 分子與細胞生物學研究所 === 103 === Gastric cancer is one of the most common causes of cancer deaths worldwide. Since the treatment strategies for gastric cancer are controversial, development of efficient therapeutic agents is important for gastric cancer. Tanshinone IIA (TIIA) is a diterpene quinone extracted from the traditional herbal medicine, Danshen (Salvia miltiorrhiza), and has been reported to have anti-tumor potential against several cancers. We previously found that TIIA could kill gastric cancer AGS cells. However, the signaling changes underlying TIIA-treated gastric cancer cells are still unclear. In this study, we applied a time-dependent phosphoproteomic approach to reveal the regulatory effects of TIIA in AGS cells. Our results showed that a total of 1092 phosphoprotiens and 3332 phosphopeptides were identified in 3615 phosphorylation sites and 349 phosphosites corresponding to 220 phosphorylated proteins were significantly regulated. By using bioinformatics analysis, we found that TIIA might regulate several cellular processes of gastric cancer cells, such as transcription mRNA processing, DNA damage and protein unfolding responses. We also reveal time course of the biological processes with TIIA treatment in AGS cells. In addition, DNA damages and protein unfolding response still occur in AGS cells for the long-termed period. Finally, we further validated that TIIA may cause the protein unfolding response and DNA damage via inducing ROS production. These findings not only uncover the molecular mechanisms mediated by TIIA but also contribute to the development of gastric cancer therapy.