Roles of Lipid Peroxidation-Derived Electrophiles in Pathogenesis of Colonic Inflammation and Colon Cancer.

Lei Lei,Eric A Decker,Jianan Zhang,Guodong Zhang

doi:10.3389/fcell.2021.665591

Abstract

Redox stress is a common feature of gut disorders such as colonic inflammation (inflammatory bowel disease or IBD) and colorectal cancer (CRC). This leads to increased colonic formation of lipid-derived electrophiles (LDEs) such as 4-hydroxynonenal (4-HNE), malondialdehyde (MDA), trans, trans-2,4-decadienal (tt-DDE), and epoxyketooctadecenoic acid (EKODE). Recent research by us and others support that treatment with LDEs increases the severity of colitis and exacerbates the development of colon tumorigenesis in vitro and in vivo, supporting a critical role of these compounds in the pathogenesis of IBD and CRC. In this review, we will discuss the effects and mechanisms of LDEs on development of IBD and CRC and lifestyle factors, which could potentially affect tissue levels of LDEs to regulate IBD and CRC development.

Highlights

Colonic inflammation and colorectal cancer (CRC) are serious health problems in many countries
Our results showed that systematic, short-time, treatment with low doses of these compounds increased the severity of dextran sodium sulfate (DSS)-induced colitis and exacerbated the development of azoxymethane (AOM)/DSS-induced colon tumorigenesis in mice, supporting a critical role of these compounds in the development of IBD and CRC in vivo (Wang et al, 2019a, 2020; Lei et al, 2021)
Clinical studies showed a strong association between lipid-derived electrophiles (LDEs) and transforming growth factor β1 (TGF-β1) levels, related to the tumor malignancy (Tüzün et al, 2012). 4-HNE may make an important contribution toward upregulating TGF-β1 expression (Leonarduzzi et al, 1997)

Summary

Introduction

Colonic inflammation (inflammatory bowel disease or IBD, including Crohn’s disease and ulcerative colitis) and colorectal cancer (CRC) are serious health problems in many countries. The incidence and prevalence of IBD have dramatically increased in the United States and other countries (Molodecky et al, 2012). IBD patients have increased risks of developing CRC (Terzić et al, 2010). There are ~147,950 new cases of CRC in the United States in 2020. The majority of these cases occurred in individuals at an age of 50 years and older, ~12% new cases of CRC were diagnosed in individuals aged younger than 50 years (Siegel et al, 2020). It is of critical importance to better understand the pathological components involved in the development of IBD and CRC, in order to develop novel strategies for prevention and/or treatment

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Results

Conclusion