Abstract 2113: Arsenic hexoxide inhibits NF-κB activity through, at least in part, suppression of IκBα phosphorylation in MCF-7 human breast cancer cells.

Abstract

Abstract Arsenic hexoxide (As4O6) has been used in Korean folk remedy for the treatment of cancer since the late 1980’s. Evidence suggests that the anti-cancer effects of As4O6 are different from those of As2O3. Nuclear factor-κB (NF-κB) is a well-known transcription factor involved in cell proliferation, invasion and metastasis. Here, we investigated the effects of As4O6 on NF-κB activity, NF-κB-regulated gene expressions, and NF-κB-mediated cellular responses. As4O6 suppressed NF-κB activation induced by TNF-α, and the some of the downstream NF-κB-regulated proteins involved in caner proliferation, metastasis and anti-apoptosis. As4O6 also suppressed IκB phosphorylation in a time-dependent manner, suggesting the suppression of NF-κB results from at least in part by inhibiting IκB degradation. We also confirmed the anti-NF-κB activity of As4O6 with synergism with TNF-α at the molecular levels. This study demonstrates that As4O6 inhibits NF-κB activation and NF-κB regulated proteins at least in part through the inhibition of IκB phosphorylation. [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) (20120002631).] Keywords: Arsenic hexoxide, Nuclear factor-κB, IκB, cancer Citation Format: Won Sup Lee, Min Jeong Kim, Ji-Hyun Jung, Jeong Won Yun, Jing Nan Lu, Sang mi Yi, Hye Jung Kim, Seong-Hwan Chang, GonSup Kim, Soon Chan Hong, Woo song Hwa. Arsenic hexoxide inhibits NF-κB activity through, at least in part, suppression of IκBα phosphorylation in MCF-7 human breast cancer cells. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 2113. doi:10.1158/1538-7445.AM2013-2113