Abstract 2263: Change in miRNA by suberoylanilide hydroxamic acid affects lung cancer cell death via regulating thioredoxin

Abstract

Abstract Suberoylanilide hydroxamic acid (SAHA) is a histone deacetylase (HDAC) inhibitor to have the anti-tumor effect. Here, we evaluated the anti-growth effect of SAHA on lung cancer (A549, SK-LU-1, HCC-95, HCC-1588, NCI-H460, NCI-H1299, Calu-6, HCC-33, NCI-H69) and normal lung (human small airway epithelial cells and human pulmonary fibroblast) cells in relation to reactive oxygen species (ROS) and thioredoxin (Trx) levels. SAHA inhibited the growth of lung cancer cells, and induced a G2/M phase arrest and apoptotic cell death in these cancer cells. In contrast, SAHA did not significantly inhibit the growth of normal lung cells and induce apoptotic cell death. Concerning the oxidative stress, SAHA increased ROS levels in lung cancer cells and induced glutathione (GSH) depletion. Moreover, it decreased the expression level of Trx1 in lung cancer cells. While the overexpression of Trx1 attenuated death and GSH depletion in SAHA-treated lung cancer cells, the downregulation of Trx1 intensified those in these cells. In addition, SAHA increased miR-629 level in lung cancer cells. The mRNA level of Trx1 was decreased by SAHA. Furthermore, the 3′ UTR region of Trx1 was regulated by miR-629. In conclusion, SAHA inhibited the growth of lung cancer cells via cell cycle arrest and apoptosis. The growth inhibition was related to the levels of Trx1 and miR-629. This work was supported by the National Research Foundation of Korea (NRF) grant funded by the Korea government (MSIP) (No. 2008-0062279) and supported by the Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education, (2013006279). Citation Format: Bo Ra You, Bo Ram Han, Woo Hyun Park. Change in miRNA by suberoylanilide hydroxamic acid affects lung cancer cell death via regulating thioredoxin. [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 2263. doi:10.1158/1538-7445.AM2014-2263