Abstract 606: Inhibition of epithelial to mesenchymal transition and advancement of therapeutic effect in oral cancer by the flavonoid compound, Quercetin: pivotal roles of Snail repression and RKIP induction.

Abstract Oral squamous cell carcinoma (OSCC) is prevalent worldwide, and survival in OSCC has not improved significantly in the last few decades. Cancer prevention using natural products has become an integral part of cancer control. Quercetin is a plant-derived flavonoid known to possess anti-inflammatory property, but its use as a chemopreventive substance has been reviewed quite recently. Several reports have assessed the pro-apoptotic action of Quercetin in cancer cells similar to many other flavonoids, although the mechanisms involved are not clear. We here reported that Quercetion-mediated sensitization may result from modulation of the EMT inducer Snail and the EMT suppressor/ immunosurveillance cancer gene product Raf-1 kinase inhibitory protein (RKIP). Quercetin regulated EMT, invasion, cell survival and apoptosis via inhibition of NF-κB inactivation as well as leaded to the induction of RKIP through downregulation of its transcriptional repressor Snail. Quercetin-induced RKIP upregulation potentiates further modulated mitochondria-mediated apoptosis, thus leading to enhance therapeutic effect. These findings demonstrate the role of Quercetin in the regulation of EMT via inhibition of NF-κB and Snail and induction of RKIP and also identified Quercetin as targets for resistance via NF-κB/Snail/RKIP circuitry. Citation Format: Yun-Ching Chang, Shih-Hwa Chiou, Shin Nieh. Inhibition of epithelial to mesenchymal transition and advancement of therapeutic effect in oral cancer by the flavonoid compound, Quercetin: pivotal roles of Snail repression and RKIP induction. [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 606. doi:10.1158/1538-7445.AM2013-606