Abstract 4777: Triptolide inhibits Wnt signaling due to DNA methylation alteration that is determined by dynamic histone 3 K79 lysine methylation in NSCLC

Abstract

Abstract Epigenetic alterations including DNA methylation and histone modifications have been associated with virtually every step of tumor development and progression. This realization has triggered an impressive quest for the development of “epigenetic drugs” and epigenetic therapies. Here we present data demonstrating that triptolide, with a unique mechanism, has anticancer effect in lung cancer development and progression. With the use of our unique non-small cell lung cancer (NSCLC) mouse model (ED160, Fen1 mutation), data shows triptolide decreases lung cancer incidence from 70% to 10%. In addition, triptolide effectively inhibits lung cancer growth and metastasis in NSG mouse Xenograft. Triptolide inactivates Wnt signaling by restoring WIF1 expression which is due to WIF1 gene demethylation. Furthermore, we revealed histone 3 lysine methylation alteration determines DNA methylation status by the communication between DNMT1 and histone 3. Together, these evidences indicated that sequential histone and DNA methylation active Wnt signaling; further it contributes to NSCLC development and progression. This discovery potentially is yielding epigenetic therapeutic opportunities for NSCLC. Note: This abstract was not presented at the meeting. Citation Format: Youqiang Li, Binghui Shen, Jae Kim, Dan Raz. Triptolide inhibits Wnt signaling due to DNA methylation alteration that is determined by dynamic histone 3 K79 lysine methylation in NSCLC. [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 4777. doi:10.1158/1538-7445.AM2015-4777