The Roles of p38 MAPK and SUMOs in Arsenic Trioxide-induced Apoptosis

• Main Authors: Te-Chung Chen, 陳得中
• Other Authors: Angela Chen
• Format: Others
• Language: en_US
• Published: 2013
• Online Access: http://ndltd.ncl.edu.tw/handle/qah6ya

碩士 === 國立中山大學 === 生物醫學研究所 === 101 === Arsenic trioxide (ATO), an anti-cancer drug for acute promyelocytic leukemia (APL), was able to induce apoptosis in several cancer cell lines including solid tumors, myeloma and lymphoma. Previous researches showed that ATO triggered apoptosis via p38 MAPK pathway, and p38 was activated by environmental stress such as ROS. Our previous studies have established that phosphorylation of p38 was elevated in AGS cells during Helicobacter pylori (Hp) infection and overexpression of SUMO-1. Moreover, SUMO-1 was co-localized with p-p38 in nucleus during overexpression of SUMO-1. In this study, we evaluated the mechanisms and the association of SUMOs and p38 of ATO-induced apoptosis. Present results exhibited that ATO induced apoptosis, and elevated p38 and SUMOs in transcript and protein levels. In addition, up-regulation of p-p38, p53, BAX, cleaved caspase 8 and t-BID were also observed during exposure of ATO. Moreover, inhibitors of p38 and caspase 8 and ROS scavenger, N-acetyl-cysteine (NAC), protected AGS from ATO-induced apoptosis. These results suggested that ATO triggered apoptosis via ROS-, p38- and caspase 8-mediated pathway. Furthermore, our data established that SUMOs enhanced p38-mediated apoptosis.