Abstract 1339: Endoplasmic reticulum stress mediates Tanshinone I induced apoptosis in mesothelioma cells

Abstract Malignant Mesothelioma (MM) is a highly aggressive tumor caused by asbestos exposure with poor survival rate. Here, we investigated anti-cancer mechanism of Tanshinone I on mesothelioma cells. Tanshinone I exerted significant cytotoxicity in a time and dose dependent manner in mesothelioma cell lines such as MSTO-211H, H28, and H2452 cells, but not in MeT-5A cells. Also, Tanshinone I increased sub-G1 population and TUNEL positive stained cells in three mesothelioma cells. Consistently, Tanshinone I cleaved poly(ADP)-ribose polymerase (PARP) and attenuated the expression of pro-caspase9, pro-caspase3 and Bcl2 as well as the phosphorylation of JNK and PI3K in three mesothelioma cells. Furthermore, Tanshinone I exerted significant cytotoxicity in a time and dose dependent manner in mesothelioma up-regulated the expression of endoplasmic reticulum (ER) stress markers such as CHOP, GRP78, ATF4, and IRE-1 in three mesothelioma cells. The apoptotic ability of Tanshinone I to cleave PARP and activate caspase 9/3 in in three mesothelioma cells. Overall, these findings suggest that Tanshinone I exhibits anti-tumor effect in MSTO-211H, H28, and H2452 cells via up-regulation of ER stress signaling as a potent anticancer agent for the mesothelioma cells. Citation Format: JiHyun Lee, Bonglee Kim. Endoplasmic reticulum stress mediates Tanshinone I induced apoptosis in mesothelioma cells. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 1339. doi:10.1158/1538-7445.AM2014-1339