Mechanisms of Rotenone-induced Apoptosis in MCF7 Human Breast Cancer Cells

• Main Authors: Yea-Tzy Deng, 鄧雅姿
• Other Authors: 林仁混
• Format: Others
• Language: en_US
• Published: 2007
• Online Access: http://ndltd.ncl.edu.tw/handle/56937066484877903129

碩士 === 國立臺灣大學 === 生物化學暨分子生物學研究所 === 95 === Rotenone, an inhibitor of NADH dehydrogenase complex, is a naturally occurring insecticide, and it is capable of inducing apoptosis. However, little is known about the mechanism for the induction of apoptosis by rotenone. Here we report that in vitro treatment of human breast cancer MCF7 cells with rotenone decreased cell viability and induced cell death in a dose- and time-dependent manner. DNA flow cytometric analysis and staining of nuclear chromatin indicated that rotenone actively induced apoptosis in MCF7 cells. Loss of mitochondrial transmembrane potential and reactive oxygen species (ROS) generation were also detected by flow cytometry. We used Western blot analysis to evaluate the apoptosis-related proteins in MCF7 cells. The levels of procaspase-9, poly (ADP-ribose) polymerase (PARP), and Bcl-2 were decreased in a time-dependent manner, while the level of Bax was increased. These findings suggest that rotenone-induced apoptosis may be a caspase- and mitochondrial-dependent pathway. Furthermore, rotenone treatment induces phosphorylation of extracellular signal-regulated kinases (ERK1/2), N-terminal protein kinase (JNK), and the p38 mitogen activated protein (MAP) kinase, indicated that ERK1/2, JNK and p38 MAP kinases are activated. Taken together, this study demonstrated rotenone as an inhibitory agent against human breast cancer MCF7 cells in vitro. Further in vivo studies are required to determine whether rotenone could be an effective chemotherapeutic agent for the management of breast cancers.