The X-linked inhibitor of apoptosis (XIAP) is a promising new molecular target for the design of novel anticancer drugs aiming at overcoming apoptosis-resistance of cancer cells to. Recent studies demonstrated that the BIR3 domain of XIAP where caspase-9 and Smac proteins bind is an attractive site for designing small-molecule inhibitors of XIAP. Embelin, identified primarily from the Embelia ribes plant, is one such compound shown to exhibit chemopreventive, anti-inflammatory, and apoptotic activities via inhibiting XIAP activity. In this study we found tthat embelin generated a dose dependent Reactive oxygen species (ROS) in PTC cell lines. Pretreatment of PTC cell with N-acetyl-Lcysteine, an scavenger of ROS prevented embelin mediated inhibition of cell proliferation and apoptosis. Further more, NAC pretreatment also abrogated embeling mediated mitochondrial apoptosis. In addition treatment of PTC cell lines with embelin causes activation of p38, a stress related map kinases leading to up-regulation of death receptor 5 (DR5). Interestingly NAC pretreatment prevented its activation as well as up-regulation of DR5. Altogether, these data suggest a novel function for embelin causes inhibition of cell proliferation and induction of apoptosis via generation of ROS a suppressor of XIAP pathway via generation of ROS in PTC cells, and raise the possibility that this agent may have a future therapeutic role in PTC and possibly other malignancies with up-regulated XIAP pathway.

Citation Format: Shahab Uddin, Maqbool Ahmed, Azhar R. Hussain, Khawla S. Al-Kuraya. Embelin induces reactive oxygen species-mediated apoptosis in PTC 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 593. doi:10.1158/1538-7445.AM2013-593

©2013 American Association for Cancer Research
2013