Impact of Epa and Dha Supplementation and 15-Lox-1 Expression On Colitis and Colitis-Associated Colorectal Cancer

<p>Inflammatory bowel disease (IBD) patients not only suffer from colitis but also from increased morbidity and mortality of colitis-associated colorectal cancer (CAC). The enzyme 15-lipoxygenase-1 (15-LOX-1) is crucial to converting omega-3 fatty acid derivatives eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) to resolvins, potent anti-inflammatory products. 15-LOX-1 effects on the conversion of EPA and DHA to resolvins that subsequently exert anti-inflammatory and anti-tumorigenic effects have received little attention. To address this knowledge gap, we hypothesize that 15-LOX-1 expression in colonic epithelial cells is essential for resolvin biosynthesis from EPA and DHA to modulate immunophenotype, limit inflammation, promote resolution, and help prevent colitis and CAC. Mice were treated with dextran sodium sulfate (DSS) alone only to induce acute and chronic colitis, or with DSS following an azoxymethane injection to induce CAC. In the chronic colitis model, DHA diet and/or expression of 15-LOX-1 reduced inflammation and altered immune cell populations. In the CAC model, DHA reduces tumor numbers by 54% in the WT/DHA group and by 52% in the 15-LOX-1/DHA group. Increased levels of 17-HDHA, RvD1, RvD4, and RvD5 in the 15-LOX-1/DHA group were inversely correlated to tumor number. EPA diet with and without expression of 15-LOX-1 reduced tumors by 47-48%. In conclusion, our study strongly supports the critical role of 15-LOX-1 for RvD production from DHA. CAC suppression occurred with DHA supplementation with and without 15-LOX-1 transgenic expression and seems to be less dependent on the production of RvDs. Further in-depth mechanistic studies are therefore needed to be better define the role of resolvins in CAC and colonic tumorigenesis in general.</p>

Name thesis:degree_name

Masters of Science (MS)

Level thesis:degree_level

Thesis (MS)

Year dc:date.available

2020

Authors dc:creator

• Jaoude, Jonathan
• <p>0000-0002-0880-4906</p>

Contributors dc:contributor

• Dr. Imad Shureiqi
• Dr. Peiying Yang
• Dr. David Volk

• colorectal cancer (CRC)
• colitis-associated colorectal cancer (CAC)
• inflammatory bowel disease (IBD)
• polyunsaturated fatty acid (PUFA)
• azoxymethane (AOM)
• dextran sodium sulfate (DSS)
• docosahexaenoic acid (DHA)
• eicosapentaenoic acid (EPA)
• E/D-series resolvins (RvE/D)
• 15-lipoxygenase-1 (15-LOX-1)
• Biology
• Cancer Biology
• Immunopathology
• Lipids
• Medicine and Health Sciences

Repository record dc:identifier

https://digitalcommons.library.tmc.edu/utgsbs_dissertations/1008

OAI identifier oai:identifier

oai:digitalcommons.library.tmc.edu:utgsbs_dissertations-2058