Abstract

Abstract Arsenic hexaoxide (As4O6) has been used as a folk remedy for the treatment of cancer since the late 1980's in Korea, and evidence suggests that As4O6-induced cell death pathway was different from that of As2O3. Here, we investigated the anticancer activities of As4O6 on SW620 human colon cancer cells. As4O6 induced cell death in a dose-dependent manner. The cell death was caspase-independent. In addition, the apoptosis was associated with suppression of p-Akt and activation of p-P38. As4O6 suppressed TNF-induced NF-κB activation through suppression of phosphorylation of IαB. As4O6 also suppressed NF-κB-regulated genes (Bcl-2, XIAP, and Bcl-xL) which are involved in anti-apoptosis. In animal experiments, As4O6 inhibited tumorigenicity of SW620 cells in a xenograft mouse model without showing any harmful effects on mice. As4O6 significantly inhibited intratumoral microvessel density. However, the inhibitory effects of As4O6 on NF-κB was minimal. In summary, in vitro study indicates that the As4O6 have anti-cancer effects on SW620 human colon cancer cells through inducing apoptosis by inhibiting anti-apoptotic molecules and in vivo study suggested that As4O6 should have additional anti-angiogenic activity. This study provides the evidence that As4O6 might be useful in the treatment of human colon cancer. [This study was supported by a grant from the National R&D Program for Cancer Control, Ministry for Health, Welfare & Family Affairs, Republic of Korea (0820050), and National Research Foundation of Korea (NRF) grant funded by the Korea government (MEST) (No. 2011-0007389)] Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 3818. doi:1538-7445.AM2012-3818

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