Study on Resveratrol-induced Changes in Mitochondrial Mass and Function with Growth Inhibition of Human Breast Cancer Cells

• Main Authors: Chin-Wen Shih, 施晉文
• Other Authors: Hsin-Chen Lee
• Format: Others
• Language: zh-TW
• Published: 2012
• Online Access: http://ndltd.ncl.edu.tw/handle/04116906719803017554

碩士 === 國立陽明大學 === 藥理學研究所 === 100 === In Taiwan, the incidence rate of breast cancer is increasing gradually in recent years, even there are many therapies to treat it, but the mortality rate still ranks the 4th in female. Therefore, to develop a new therapy to increase the therapeutic response is urgently needed. The defect of mitochondrial function is observed in many human cancers, including breast cancer. Besides, many gene mutations take part in the development of cancers and alter the energy metabolism. Resveratrol is a natural polyphenol compound found in many plants. Its chemopreventive and chemotherapeutic properties have been reported in various human cancers, and have been reported to improve mitochondrial function through the SRIT1/PGC-1α pathway. Thus, the purpose of this study was to investigate the relationship between growth inhibition by resveratrol and the role of mitochondrial alteration in human breast cancer cells. Three kinds of human breast cancer cell lines, MDA-MB-231, MCF-7 and BT-474 were used for this study, and these breast cancer cell lines are different in the estrogen receptor (ER) , progesterone receptor (PR) and epidermal growth factor receptor 2 (HER2) expression level, as well as p53 mutation status. Firstly, three breast cancer cell lines were treated with resveratrol at different concentrations and time points, and it was observed that growth inhibition in low concentrations, 25 and 50 μM, after short time, 24 and 48 hours, treatment and cell death in high concentration, 100 and 200 μM, after long time, 48 and 72 hours, treatment by resveratrol. The three cell lines displayed different sensitivities to resveratrol treatment, BT-474 had the lowest sensitivity to resveratrol. The low concentrations, 25 and 50 μM, of resveratrol were chosen in all experiments in this study. The results revealed that resveratrol increased mitochondrial mass, increased oxygen consumption rate and hydrogen peroxide content of human breast cancer cells. Moreover, the intracellular ATP was increased in MDA-MB- 231 and MCF-7 after treatment with resveratrol. Furthermore, the gene expression level of PGC-1α was induced by resveratrol in MDA-MB-231 and MCF-7, and the protein expression level of Complex IV subunits was increased in three breast cancer cell lines. Taken together, these results suggest that low dose, 25 and 50 μM, resveratrol treatment in human breast cancer cells could induce the mitochondrial function and inhibit breast cancer growth, which might provide a potential therapeutic strategy for treatment of human breast cancer.