Molecular mechanisms of α-mangostin on apoptosis in human cervical cancer cells

• Main Authors: Shiua-Hua Wen, 文孝華
• Other Authors: 謝逸憲
• Format: Others
• Language: zh-TW
• Published: 2014
• Online Access: http://ndltd.ncl.edu.tw/handle/783cev

碩士 === 中山醫學大學 === 生化暨生物科技研究所 === 102 === The mangosteen is a xanthone derivative shown to have antioxidant and anticarcinogen properties. α-mangostin is a flavonoid that has been shown to have anticancer, antiinvasive and apoptosis properties in various types of human cancer cells. The aim of this study was to investigate the mechanism of apoptosis induced by α-mangostin on human cervical carcinoma cells. In this study, HeLa and SiHa cell lines were treated with α-mangostin to suggest that α-mangostin induces apoptosis and by MTT assay, DAPI stain, annexin-V assay, α-mangostin triggered the activations of caspases-3, -9, and PARP, resulting in apoptosis induction. Furthermore, treatment with α-mangostin resulted in a loss of mitochondrial membrane potential (MMP), and augmented the Bax/Bcl-2 ratio. We also found that α-mangostin induces ROS release, added the ROS inhibitor (NAC) significantly abolished the α-mangostin-induced apoptosis, loss of MMP and apoptosis related-protein activation. Moreover, treatment of HeLa cells with α-mangostin induced a sustained activation of the phosphorylation of p38, and inhibition of p38 by SB203580 or transfection with the siRNA-p38 significantly abolished the α-mangostin-induced apoptosis through induction of apoptosis, loss of MMP and apoptosis related-protein activation. Finally, in vivo xenograft mice experiments revealed that α-mangostin significantly reduced tumor growth in mice with HeLa tumor xenografts. Taken together , that α-mangostin induces cell death by generation of ROS, and activation of p38 MAPK, and executed through mitochondrial mediated caspase pathway. Our results suggest that α-mangostin may be potentially used as anti-cancer agents in human cervical cancer.