Study of the mechanism of estradiol metabolite 2-methoxyestradiol on the anti-metastasis and inducing apoptosis of breast cancer cells

• Main Authors: Pei-Chia, 王貝嘉
• Other Authors: 鄭鈞文
• Format: Others
• Language: zh-TW
• Published: 2008
• Online Access: http://ndltd.ncl.edu.tw/handle/01259586792768230836

碩士 === 中山醫學大學 === 生化暨生物科技研究所 === 96 === 2-Methoxyestradiol (2-MetE2), an endogenous estrogen metabolite of 17-beta estradiol, has been reported to effect on suppression of tumor cell malignancy. However, the molecular mechanisms underlying 2-MetE2 on growth inhibition, metastasis and apoptosis induction are still unknown. The aim of this study is to investigate the anti-tumor effects of 2-MetE2 in human breast cancer cells. Compared with untreated controls, treatment of Hs578T cells with 2-MetE2 increased chromatin condensation, DNA fragmentation and cell apoptosis. 2-MetE2 exposure resulted in collapse of mitochondrial membrane potential, accompanied by altered ratio of Bax/Bcl-2, release of cytochrome c and activation of caspase-9/3. In addition, 2-MetE2 inhibited cell invasiveness and migration on Hs 578T cells through decreased activity of matrix metalloproteinase 2 (MMP-2) was ascribed to IkB kinase inactivation. Treatment of 2-MetE2 resulted in an inhibition of the PI3K-Akt/PKB survival pathway in Hs 578T cells. Moreover, prohibition of cell proliferation on 2-MetE2-treat Hs 578T cells through decreased of cyclin D, cyclin E, cyclin A and cyclin B expression. In conclusion, our study of the effect on 2-MetE2 on anti-proliferation, anti-invasion, anti-migration, and apoptosis suggests that 2-MetE2 is a potential agent for treating breast cancer.