Abstract 5202: Magnolin suppresses cell migration by abrogation of ERK-mediated RSK2/NF-κB signaling pathway

Abstract

Our previous study demonstrated that RSK2 directly phosphorylated IκBα at ser 32, resulted in its degradation which leads to promote NF-κB activation and might be an important role in metastasis. Therefore, it is reasonable the discovery of chemotherapeutic and/or chemopreventive agent. Magnolin, an ingredient of magnolia species, suppressed EGF-induced neoplastic cell transformation by targeting of ERK 1 and 2. In this study, we found that magnolin inhibited cell migration and invasion of normal cell and human lung cancer cells. Further, we demonstrated that magnolin suppressed epidermal growth factor-induced ERK/RSK2 signaling pathway, resulting in suppression of NF-κB activity in JB6Cl41 cells. The EGF-induced NF-κB activity was abrogated up-regulation of COX-2 mRNA expression and COX-2 protein levels by co-treatment of EGF and magnolin. Interestingly, magnolin suppressed ERK-mediated MMP-2 and NF-κB-mediated MMP-9 expression. In addition, we found that the protein expression of N-cadherin involved in metastasis was markedly attenuated upon treatment with magnolin. Notably, magnolin suppressed the migration and invasion of lung cancer cells in a dose-dependent manner. Taken together, these results demonstrated that magnolin is beneficial for the anti-invasion and -migration in cancer metastasis. Citation Format: Cheol-Jung Lee, Mee-Hyun Lee, Ji-Hong Song, Sun-Mi Yoo, Yong-Yeon Cho. Magnolin suppresses cell migration by abrogation of ERK-mediated RSK2/NF-κB signaling pathway. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 5202. doi:10.1158/1538-7445.AM2015-5202