title: 4-Hydroxynonenal metabolites and adducts in pre-carcinogenic conditions and cancer.
abstract: 4-hydroxy-2-nonenal (HNE) is an amazing reactive compound, originating from lipid peroxidation within cells but also in food and considered as a "second messenger" of oxidative stress. Due to its chemical features, HNE is able to make covalent links with DNA, proteins and lipids. The aim of this review is to give a comprehensive summary of the chemical properties of HNE and of the consequences of its reactivity in relation to cancer development. The formation of exocyclic etheno-and propano-adducts and genotoxic effects are addressed. The adduction to cellular proteins and the repercussions on the regulation of cell signaling pathways involved in cancer development are reviewed, notably on the Nrf2/Keap1/ARE pathway. The metabolic pathways leading to the inactivation/elimination or, on the contrary, to the bioactivation of HNE are considered. A special focus is given on the link between HNE and colorectal cancer development, due to its occurrence in foodstuffs and in the digestive lumen, during digestion.
authors.affiliation: Toxalim (Research Centre in Food Toxicology), Université de Toulouse, INRA, ENVT, INP-Purpan, UPS, Toulouse, France. Electronic address: Francoise.Gueraud@inra.fr.
authors.forename: Françoise
authors.initials: F
authors.lastname: Guéraud
mesh_terms: D000447:Aldehydes / Q000378:metabolism*; D063646:Carcinogenesis / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D003106:Colon / Q000378:metabolism / Q000473:pathology; D015179:Colorectal Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D018736:DNA Adducts / Q000096:biosynthesis*; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D015212:Inflammatory Bowel Diseases / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D000072019:Kelch-Like ECH-Associated Protein 1 / Q000235:genetics / Q000378:metabolism; D020928:Mitogen-Activated Protein Kinases / Q000235:genetics / Q000378:metabolism; D051267:NF-E2-Related Factor 2 / Q000235:genetics / Q000378:metabolism; D010084:Oxidation-Reduction; D018384:Oxidative Stress; D011230:Precancerous Conditions / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D011493:Protein Kinase C / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction
chemical_list: D000447:Aldehydes; D018736:DNA Adducts; C431364:KEAP1 protein, human; D000072019:Kelch-Like ECH-Associated Protein 1; D051267:NF-E2-Related Factor 2; C495635:NFE2L2 protein, human; D011493:Protein Kinase C; D020928:Mitogen-Activated Protein Kinases; C027576:4-hydroxy-2-nonenal
keywords: 4-hydroxynonenal; Cancer; Colorectal cancer; Electrophilic; Etheno-adducts; GST; Genotoxicity; Heme iron; Keap1; Lipid peroxidation; Mercapturate; Nrf2; Oxidative stress; Propano-adducts