Work

Repurposing the anti-malarial drug, quinacrine: new anti-colitis properties

Year: 2016

Type: article

Abstract: // Alexander A. Chumanevich 1 , Erin E. Witalison 1 , Anusha Chaparala 1 , Anastasiya Chumanevich 1 , Prakash Nagarkatti 2 , Mitzi Nagarkatti 2 and Lorne J. Hofseth 1 1 Department of Drug Discovery and Biomedical Sciences, South Carolina College of Pharmacy, University of South Carolina, Columbia, SC, USA 2 School of Medicine, University of South Carolina, Columbia, SC, USA Correspondence to: Lorne J. Hofseth, email: // Keywords : quinacrine, colitis, inflammation, dextran sulfate sodium, oxazolone Received : June 08, 2016 Accepted : June 15, 2016 Published : July 14, 2016 Abstract Background: Ulcerative colitis (UC) is a chronic inflammatory bowel disease that is associated with an increased risk of colorectal cancer in 8-10 years after disease onset. Current colitis treatment strategies do not offer a cure for the disease, but only treat the symptoms with limited success and dangerous side-effects. Also, there is no preventive treatment for either UC or colorectal cancer. Quinacrine is an anti-malarial drug with versatile use in the treatment of diseases involving inflammatory response such as rheumatoid arthritis and lupus erythematosus. It also has putative anti-cancer effect. Quinacrine’s anti-inflammatory, anti-oxidant properties, and anti-tumorigenic properties make it a potential small molecule preventive agent for both UC and associated colorectal cancer. Results: There were obvious changes in the CDI, histology, and inflammatory load in quinacrine-treated groups in a dose and time dependent manner in both models of UC, induced by chemical or haptenating agent. Methods: We tested quinacrine at two different doses as a colitis treatment agent in two mouse models of UC - the dextran sulfate sodium and oxazolone. The clinical disease index (CDI), histological changes of the colon, levels of inflammatory markers (Cox-2, iNOS, p53) and overall health vitals were evaluated. Conclusions: We demonstrate that quinacrine successfully suppresses colitis without any indication of toxicity or side-effects in two mouse models of UC.

Source: Oncotarget

DOI: 10.18632/oncotarget.10608