Abstract 5503: Panaxynol, a potential treatment for colitis, selectively targets pro-inflammatory macrophages for DNA damage and apoptosis

Abstract

Abstract Ulcerative colitis (UC) is a chronic inflammatory bowel disease (IBD) that has been associated with a high risk for colorectal cancer. Since available conventional treatments provide mostly modest relief and are paired with a high risk of side effects, complementary and alternative medicines (CAMs) can offer a safe and effective option for the treatment of IBD. Earlier studies in our lab have shown that American Ginseng can suppress colitis and also prevent colitis-associated colon cancer in mice. During the process of isolating active ingredients from this plant, Panaxynol was identified as a key component. Panaxynol has been shown to have anti-cancer and anti-inflammatory properties, but it has not been studied in macrophage-driven autoimmunity models. Here, we study the effects of Panaxynol on macrophages and other cell lines in an attempt to understand its mechanism of action. We show that Panaxynol induces DNA damage and apoptosis in macrophages in a dose-dependent manner using phosphorylated γ-H2AX detection and TUNEL assays, respectively. Importantly, DNA damage and apoptosis were induced in other cell types (e.g. epithelial cells and fibroblasts) only when using higher doses of Panaxynol (>50μM). Co-culture experiments confirm that Panaxynol selectively targets macrophages in the presence of colon cancer cells. To explore mechanisms, we asked whether Panaxynol inhibits the STAT1 pathway. Results showing an inhibition of STAT1 phosphorylation are consistent with the hypothesis. We plan to extend these studies to an in vivo mouse model of DSS-induced colitis in order to understand the anti-inflammatory mechanisms of Panaxynol. Positive outcomes from this study can potentially serve as a model for the treatment of colitis and other autoimmune diseases (at least partly) associated with macrophage dysfunction. Citation Format: Anusha Chaparala, Deepak Poudyal, Xiangli Cui, Bin Li, Erin E. Witalison, Taixing Cui, Lorne J. Hofseth. Panaxynol, a potential treatment for colitis, selectively targets pro-inflammatory macrophages for DNA damage and apoptosis. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 5503. doi:10.1158/1538-7445.AM2015-5503