title: Actions of vitamin D are mediated by the TLR4 pathway in inflammation-induced colon cancer.
abstract: Many chronic inflammatory diseases are associated with increased risk of developing cancer. In the colon, strong support for a link between chronic inflammation and cancer extends, in part, from population-based studies of persons with inflammatory bowel disease (IBD). Patients with IBD are at increased risk of developing colorectal cancer (CRC). The general consensus is that IBD results from the combined effects of genetics and environment factors known to affect the immune system. Vitamin D, an important regulator of the immune system, has been linked to IBD. Despite the strong potential reported for 1,25-dihydroxyvitamin D (1,25-OH)2D), its effects on calcium metabolism limits its application. Recently, less active vitamin D metabolites, cholecalciferol and 25-hydroxyvitamin D (25(OH)D), have gained considerable attention as promising agents against IBD-related colon cancer. Yet, their anti-proliferative properties and mechanism of action remain to be better defined. We present several signaling pathways commonly regulated by vitamin D compounds and highlight their regulation on TLR4. The efficacy of 25(OH)D and 1alpha-hydroxyviatmin D5 are evaluated using the azoxymethane (AOM)/dextran sodium sulfate (DSS)-induced IBD-related colon carcinogenesis model. In summary, vitamin D supplementation may provide a cost-effective approach to reduce IBD related colon cancer.
authors.affiliation: Division of Carcinogenesis and Chemoprevention, IIT Research Institute, Chicago, IL 60616, USA. gmurillo@iitri.org
authors.forename: G
authors.initials: G
authors.lastname: Murillo
authors.forename: V
authors.initials: V
authors.lastname: Nagpal
authors.forename: N
authors.initials: N
authors.lastname: Tiwari
authors.forename: R V
authors.initials: RV
authors.lastname: Benya
authors.forename: R G
authors.initials: RG
authors.lastname: Mehta
mesh_terms: D018938:Caco-2 Cells; D002117:Calcitriol / Q000378:metabolism; D002762:Cholecalciferol / Q000378:metabolism; D003110:Colonic Neoplasms / Q000378:metabolism*; D019587:Dietary Supplements; D005260:Female; D045325:HCT116 Cells; D019073:HT29 Cells; D006801:Humans; D007249:Inflammation; D015212:Inflammatory Bowel Diseases / Q000378:metabolism; D008954:Models, Biological; D020411:Oligonucleotide Array Sequence Analysis; D051197:Toll-Like Receptor 4 / Q000378:metabolism*; D014807:Vitamin D / Q000378:metabolism / Q000494:pharmacology*
chemical_list: C495345:TLR4 protein, human; D051197:Toll-Like Receptor 4; D014807:Vitamin D; D002762:Cholecalciferol; D002117:Calcitriol