Abstract 1691: Apoptotic and antitumor effects of rotenone in MCF-7 human breast cancer cells are mediated ROS through activating JNK and p38 MAPK signaling

Abstract

Abstract Rotenone is a natural hydrophobic pesticide derived from the roots of Derris and Lonchorcarpus species. The pesticidal activity of rotenone is attributed to irreversible binding and inactivation of complex of the mitochondrial transport chain. This can block electron transport from complex to ubiquinone, resulting in a blockage of the oxidative phosphorylation process, and an increase of the reactive oxygen species (ROS). Rotenone has been shown to display anticancer activity through the induction of apoptosis in various cancer cells. However, the underlying mechanism is still not fully elucidated. In the present study, rotenone showed a strong growth inhibitory effect against human breast MCF-7 cells. DNA flow cytometric analysis, chromatin condensation and poly(ADP-ribose) polymerase (PARP) cleavage indicated rotenone actively induced apoptosis in MCF-7 cells. The anti-apoptotic protein BCl-2, was decreased, whereas the apoptotic protein, Bax, was increased in a time-dependent manner in rotenone-induced apoptosis. Moreover. The treatment of rotenone in MCF-7 cells caused the activation of c-jun N-terminal kinase (JNK) and p38 mitogen-activated protein kinase (MAPKs) and the inactivation of extracellular signal-regulated protein kinase1/2 (ERK1/2). The pharmacological inhibitor of JNK and p38 MAPK revealed significant protection against rotenone-induced apoptosis. In summary, these results indicate rotenone may induce apoptosis through ROS and JNK/p38MAPK activation in MCF-7 cells. In conclusion, we examines the molecular mechanism involved in rotenone-induced apoptosis in human breast cancer MCF-7 cells. We have demonstrated a sequential events that rotenone-induced apoptosis in the cells through ROS generation, which serves as a pivotal upstream function in activating JNK and p38MAPKs, which leads to a decrease of BCl-2 and increase of Bax and finally to inducing apoptosis. Note: This abstract was not presented at the AACR 101st Annual Meeting 2010 because the presenter was unable to attend. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 1691.