Investigation of anti-tumor and anti-metastatic activties of 11-epi-sinulariolide acetate from the cultured soft coral Sinularia flexibilis on hepatoma cells

• Main Authors: Lin, Jen-Jie, 林振頡
• Other Authors: Liao, Ming-Hui
• Format: Others
• Language: zh-TW
• Published: 2017
• Online Access: http://ndltd.ncl.edu.tw/handle/9b3885

博士 === 國立屏東科技大學 === 獸醫學系所 === 105 === The natural compounds from soft corals have been increasingly used for antitumor and other therapeutic purposes. 11-epi-sinulariolide acetate (terms: 11-epi-SA in this paper), an active compound isolated from the cultured soft coral Sinularia flexibilis was examined for the potential anti-tumor effect on four hepatocellular carcinoma cells (HCC). In the present study, HA22T cells showed more cytotoxic effect upon 11-epi-SA treatment as investigation the cell viability using MTT assay. Protein profiling of 11-epi-SA-treated HA22T cells revealed profound protein alterations related to stress response and protein synthesis and folding, suggesting that mitochondria and endoplasmic reticulum (ER) play a role in 11-epi-SA -initiated apoptosis. 11-epi-SA leads to the activation of caspase-dependent apoptotic cell death suggesting that mitochondrial-related apoptosis genes were involved in the cell programmed death. The unfolded protein response (UPR) signaling pathways-related proteins are also activated upon 11-epi-SA treatment and these changes were accompanied by increased expression of GADD153/CHOP, a transcription factor associated with growth arrest and apoptosis in the event of prolonged ER stress. However, the anti-migration and invasion effects and molecular mechanism of 11-epi-SA on hepatocellular carcinoma remain poorly understood. In this study, first discovered that 11-epi-SA provided a concentration-dependent inhibitory effect on the migration of human hepatocellular carcinoma HA22T cells by trans-well migration and invasion assays. Furthermore, after treatment with 11-epi-SA for 24 hours, there was suppressed the protein levels of matrix metalloproteinase-2 (MMP-2), matrix metalloproteinase-9 (MMP-9) and urokinase-type plasminogen activator (uPA) in HA22T cells. Meanwhile, the expression of tissue inhibitor of metalloproteinase-1 (TIMP-1) and metalloproteinase-2 (TIMP-2) were increased in a concentration-dependent manner. Further investigation revealed that 11-epi-SA suppressed the phosphorylation of ERK1/2 and p38MAPK. 11-epi-SA also suppressed the expression of the phosphorylation of FAK/PI3K/AKT/mTOR pathways. In the present study, we investigated the anti-migration and invasion effects and underlying mechanisms of 11-epi-SA in HA22T cells.