Oncotarget

Research Papers:

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

Alexander A. Chumanevich, Erin E. Witalison, Anusha Chaparala, Anastasiya Chumanevich, Prakash Nagarkatti, Mitzi Nagarkatti and Lorne J. Hofseth _

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Oncotarget. 2016; 7:52928-52939. https://doi.org/10.18632/oncotarget.10608

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Abstract

Alexander A. Chumanevich1, Erin E. Witalison1, Anusha Chaparala1, Anastasiya Chumanevich1, Prakash Nagarkatti2, Mitzi Nagarkatti2 and Lorne J. Hofseth1

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.


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