Dietary Modulation of Inflammation-Induced Colorectal Cancer through PPAR𝛾

Figure 1

Chronic inflammation activates pathways leading to cancer. Chronic inflammation stemming from ulcerative colitis (UC) and Crohn's disease (CD), the two clinical manifestations of inflammatory bowel disease, activates nuclear factor-𝜅B (NF-𝜅B) downstream of MyD88 through the TLR and IL-1R. In turn, NF-𝜅B activation increases the expression of pro-inflammatory cytokines IL-6 and IL-1𝛽. TNF-𝛼 also activates NF-𝜅B which, in turn, increases the expression of TNF-𝛼, leading to a positive feedback loop between TNF-𝛼 and NF-𝜅B. Chronic inflammation also leads to the production of ROS which can damage DNA which can cause mutations responsible for tumorigenesis. ROS also cause the production of IL-8, iNOS, and MMP-1, which promote tumor growth. On the other hand, activation of PPAR𝛾 can block carcinogenesis at two levels: (1) by antagonizing NF-𝜅B activity and (2) by suppressing IL-8 and iNOS expression.