Abstract 3238: Taiwanin A targets against nonsteroidal anti-inflammatory drug-activated gene-1 in human lung carcinoma

Abstract

Abstract Taiwanin A (α,β-bis(piperonylidene)-γ-butyrolactone) is isolated from Taiwania cryptomerioides. Similar to paclitaxel, Taiwanin A also extracted from tree barks and have anti-tumor activity in breast, liver, and lung cancer cell lines. The objective of this study is to demonstrate the cytotoxicity of Taiwanin A against tumor cells by increasing the expression of Non-steroidal anti-inflammatory drug-activated gene (NAG-1). NAG-1 has been reported to have antitumor and pro-apoptotic activity, suggesting potential target for cancer therapy. Silencing NAG-1 mRNA expression in A549 reduces the cytotoxicity caused by Taiwanin A. Furthermore, the c-Jun-N-terminal kinase/Ste20-related protein proline/alanine-rich kinase (JNK/SPAK) pathway played a key role in the action of NAG-1 on cell viability, whereas the addition of the JNK pathway inhibitor, SP600125, resulted in the inhibitory effect of NAG-1 and recovery of Taiwanin A treated cells. Xenograft tumor model showed that Taiwanin A dose-dependently significantly decreases tumor mediated growth in nude mice by increasing NAG-1 expression accompanied tumor apoptosis. These data support the conclusion that Taiwanin A inhibits lung carcinoma growth by increasing NAG-1 expression via the JNK pathway both in vivo and in vitro. This result might be contributed to compound design for increasing cytotoxicity activity in the future. Citation Format: Hong-Meng Chuang, Horng-Jyh Harn. Taiwanin A targets against nonsteroidal anti-inflammatory drug-activated gene-1 in human lung carcinoma. [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 3238. doi:10.1158/1538-7445.AM2015-3238