People with inflammatory bowel disease [IBD: ulcerative colitis (UC) and Crohn's disease (CD)] have a high colon cancer risk. IBDs are life-long, and start in about one third of patients during childhood. Due to recent advances in the understanding of IBD, immunosuppressive agents (mainly against TNF?), as well as other biological drugs, are being used with increasing frequency. Although this approach has improved the clinical condition of the majority of patients with moderate to severe IBD, this aggressive strategy has side effects, including severe infection, cancer and death. Therefore, finding less toxic means to suppress colitis and prevent colon cancer are of high priority. We have focused our efforts on complementary and alternative medicines, as well as small molecule inhibitors with anti-inflammatory properties to accomplish this goal. Here, we will test the hypothesis that an established small molecule anti- malarial drug, previously FDA approved for the treatment of giardiasis, malaria, and tape-worm infection, called Quinacrine, can be used to suppress colitis and prevent colon cancer associated with colitis. The rationale for this hypothesis is: (a) Quinacrine has been shown to be effective against autoimmune, chronic inflammatory diseases such as systemic lupus erythematosis, and rheumatoid arthritis;and (b) Quinacrine can suppress iNOS induction and drive apoptosis of inflammatory cells. The latter rationale stems from our published findings that agents having these properties (suppress iNOS and drive apoptosis of inflammatory cells in vitro) are likely to have efficacy in the suppression of colitis and prevention of colon cancer in vivo. Results from this study will validate the use of Quinacrine against colitis and in colon cancer prevention, provide data to explore in more detail the mechanisms by which Quinacrine does this (in a future R01 application), and add another small molecule (previously FDA approved for certain conditions) to a growing list (of small molecules) that have a high potential to suppress colitis in humans without the detrimental side effects of current approved treatments for IBD. This can potentially benefit millions of people.
Current biological therapies of inflammatory bowel disease (IBD;a high colon cancer risk disease) are fraught with side effects, including cancer and death. In our experience, agents that suppress inducible nitric oxide induction and drive apoptosis of inflammatory cells are likely to be highly efficient in suppressing colitis and preventing colon cancer. Because we found Quinacrine to be such an agent, and that others have found anti- oxidant properties of Quinacrine, here we will explore the hypothesis that Quinacrine suppresses colitis and prevents colon cancer associated with colitis.
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