HNE and cholesterol oxidation products in colorectal inflammation and carcinogenesis


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Abstract

Consistent experimental data suggest the importance of inflammation-associated oxidative stress in colorectal cancer (CRC) pathogenesis. Inflammatory bowel disease with chronic intestinal inflammation is now considered a precancerous condition. Oxidative stress is an essential feature of inflammation. Activation of redox-sensitive pro-inflammatory cell signals and inflammatory mediators concur to establish a pro-tumoral environment. In this frame, lipid oxidation products, namely 4-hydroxynonenal and oxysterols, can be produced in big quantity so as to be able to exert their function as inducers of cell signaling pathways of proliferation and survival. Notably, an important source of these two compounds is represented by a high fat diet, which is undoubtedly a risk factor for inflammation and CRC development. Current evidence for the emerging implication of these two oxidized lipids in inflammation and CRC development is discussed in this review.Graphical abstractHighlightsInflammation is a major driving force in colorectal cancer (CRC) development.Oxysterols and HNE are overproduced by colitis-associated oxidative reactions.They also originate from a high fat diet, which is a risk factor for inflammation/CRC.Accumulation of oxysterols and HNE in intestinal mucosa favor tumor growth.These oxidation compounds behave as signaling molecules in survival and proliferation.

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