Abstract
Abstract In this study, we investigated the anti-proliferative and pro-apoptotic properties of novel hydroxamic acid-derivative, MHY218, in HCT116 human colon cancer cells. We found that treatment of cells with MHY218 resulted in growth inhibition and induction of apoptosis in a concentration-dependent manner. The induction of apoptosis was showed by decreased viability, cleavage of poly(ADP-ribose) polymerase (PARP), alteration in the ratio of Bax/Bcl-2 protein expression, and activation of caspase-8 and -9 together with caspase-3. In addition, MHY218 induced G2/M phase cell cycle arrest which was related to a decrease in the protein expression of cyclin B1 and its activating partners Cdc25c and Cdc2. MHY218 also caused an increase in the expression levels of p21WAF1/CIP1 in a p53-independent pathway. Nuclear transcription factor-kappa B (NF-κB) has been reported to be an implicated factor in apoptotic cell death of various cancer cells. Therefore, we found the effect of MHY218 on NF-κB signaling pathway. Treatment of cells with MHY218 resulted in inhibition of the expression levels of NF-κB and IκBα in a dose-dependent manner. These results suggest that MHY218 may have potential as a chemotherapeutic agent for prevention against colon cancer. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 182. doi:10.1158/1538-7445.AM2011-182
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