Abstract 849: Reactive oxygen species mediated activation of AMP activated protein kinase and c-Jun N-terminal kinase plays a critical role in beta sitosterol induced apoptosis in multiple myeloma U266 cells.

Abstract

Abstract Although beta sitosterol has been well known to have anti-tumor activity in liver, lung, colon, stomach, breast and prostate cancers via cell cycle arrest and apoptosis induction, the underlying mechanism of anti-cancer effect of beta sitosterol in multiple myeloma cells was never elucidated until now. Thus, in the present study, the role of reactive oxygen species (ROS) in association with AMP-activated protein kinase (AMPK) and c-Jun N-terminal kinase (JNK) pathways was demonstrated in beta sitosterol treated multiple myeloma U266 cells. Beta sitosterol exerted cytotoxicity, increased sub-G1 apoptotic population and activated caspase-9 and -3, cleaved poly (ADP-ribose) polymerase (PARP) followed by decrease in mitochondrial potential in U266 cells. Beta sitosterol promoted ROS production, activated AMPK, acetyl-CoA carboxylase (ACC) and JNK in U266 cells. Also, beta sitosterol attenuated the phosphorylation of AKT, mammalian target of rapamycin (mTOR) and S6K, and the expression of cyclooxygenase (COX)2 and VEGF in U266 cells. Conversely, AMPK inhibitor compound C and JNK nhibitor SP600125 suppressed apoptosis induced by beta sitosterol in U266 cells. Furthermore, ROS scavenger N-acetyl-L-cysteine (NAC) attenuated beta sitosterol mediated sub-G1 accumulation, PARP cleavage, JNK and AMPK activation in U266 cells. Overall, these findings for the first time suggest that ROS mediated activation of cancer metabolism related genes such as AMPK and JNK plays an important role in beta sitosterol induced apoptosis in U266 multiple myeloma cells. Citation Format: Sun-Mi Cho, Ji-Sung Kim, Hyosook song, Eun-Jung Sohn, Ji-Hyun Kim, Ji Hoon Jung, Jung-Hyo Kim, Soo-Jin Jeong, Eun-OK Lee, HyoJeong Lee, Sung Hoon Kim. Reactive oxygen species mediated activation of AMP activated protein kinase and c-Jun N-terminal kinase plays a critical role in beta sitosterol induced apoptosis in multiple myeloma U266 cells. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 849. doi:10.1158/1538-7445.AM2013-849