Abstract
BackgroundUlcerative 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.ResultsThere 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.MethodsWe 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.ConclusionsWe demonstrate that quinacrine successfully suppresses colitis without any indication of toxicity or side-effects in two mouse models of UC.
Highlights
Ulcerative colitis (UC) is a chronic disease that causes inflammation and ulcers in the colon and the rectum
The cellular levels of nitric oxide (NO) and associated reactive nitrogen species (RNS) are driving factors of inflammation and cancers associated with chronic inflammation [20]
Western blot analysis shows that pre-incubation of ANA-1 cells with quinacrine effectively attenuates the induction of inducible nitric oxide synthase (iNOS) for up to 24 hours (Figure 1A and 1B)
Summary
Ulcerative colitis (UC) is a chronic disease that causes inflammation and ulcers in the colon and the rectum. 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. Quinacrine is an antimalarial drug with versatile use in the treatment of diseases involving inflammatory response such as rheumatoid arthritis and lupus erythematosus. Quinacrine’s anti-inflammatory, anti-oxidant properties, and antitumorigenic properties make it a potential small molecule preventive agent for both UC and associated colorectal cancer
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