title: Apple polysaccharide reduces NF-Kb mediated colitis-associated colon carcinogenesis.
abstract: Nuclear factor-kappa B (NF-κB) is an important molecule in mediating inflammatory colitis, which can lead to colorectal cancer (CRC). The aim of this study was to evaluate the chemopreventive efficacy of apple polysaccharide extract (AP) in inhibiting NF-κB-mediated inflammation pathways in CRC. We evaluated AP in vitro in HT-29 and SW620 human CRC cells. We also used the azoxymethane and dextran sodium sulphate (AOM/DSS) model to induce colon carcinogenesis in vivo. The chemoprotective effects of AP were assessed using Western blot, immunofluorescence assay, real-time PCR, electrophoretic mobility shift assay, and flow cytometry. AP reduced AOM/DSS-associated toxicities, prevented carcinogenesis, and decreased the expression of TLR4, MD2, MyD88, TRAM, TRIF-related adapter molecule, interferon-β, tumor necrosis factor-α, and interleukin-6. The protective effects of AP may be related to the inhibition of TLR4/MD2-mediated signaling, including MyD88 and TRIF, as well as the inhibition of NF-κB-mediated inflammatory signaling pathways. Therefore, AP could be used in combination therapy for the prevention of colitis-associated colon cancer.
authors.affiliation: a Department of Pathogen Biology and Immunology , Xi'an Medical University , Xi'an , China and Key Laboratory of Gastrointestinal Pharmacology of Chinese Materia Medica of the State Administration of Traditional Chinese Medicine, Department of Pharmacology, School of Pharmacy , Fourth Military Medical University , Xi'an , China.
authors.forename: Dian
authors.initials: D
authors.lastname: Zhang
authors.forename: Man
authors.initials: M
authors.lastname: Mi
authors.forename: Fengliang
authors.initials: F
authors.lastname: Jiang
authors.forename: Yang
authors.initials: Y
authors.lastname: Sun
authors.forename: Yuhua
authors.initials: Y
authors.lastname: Li
authors.forename: Libin
authors.initials: L
authors.lastname: Yang
authors.forename: Lei
authors.initials: L
authors.lastname: Fan
authors.forename: Qian
authors.initials: Q
authors.lastname: Li
authors.forename: Jin
authors.initials: J
authors.lastname: Meng
authors.forename: Zhenggang
authors.initials: Z
authors.lastname: Yue
authors.forename: Li
authors.initials: L
authors.lastname: Liu
authors.forename: Qibing
authors.initials: Q
authors.lastname: Mei
mesh_terms: D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000302:isolation & purification / Q000378:metabolism / Q000627:therapeutic use; D016588:Anticarcinogenic Agents / Q000302:isolation & purification / Q000378:metabolism / Q000627:therapeutic use*; D000972:Antineoplastic Agents, Phytogenic / Q000302:isolation & purification / Q000378:metabolism / Q000627:therapeutic use; D045744:Cell Line, Tumor; D003092:Colitis / Q000276:immunology / Q000503:physiopathology*; D003106:Colon / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D003110:Colonic Neoplasms / Q000178:diet therapy / Q000209:etiology / Q000378:metabolism / Q000517:prevention & control*; D019587:Dietary Supplements; D004195:Disease Models, Animal; D005638:Fruit / Q000737:chemistry; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007413:Intestinal Mucosa / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D008297:Male; D027845:Malus / Q000737:chemistry; D008813:Mice, Inbred ICR; D016328:NF-kappa B / Q000037:antagonists & inhibitors* / Q000378:metabolism; D009363:Neoplasm Proteins / Q000819:agonists / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D010936:Plant Extracts / Q000302:isolation & purification / Q000378:metabolism / Q000627:therapeutic use; D011134:Polysaccharides / Q000302:isolation & purification / Q000378:metabolism / Q000627:therapeutic use*; D015398:Signal Transduction
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D016588:Anticarcinogenic Agents; D000972:Antineoplastic Agents, Phytogenic; D016328:NF-kappa B; D009363:Neoplasm Proteins; D010936:Plant Extracts; D011134:Polysaccharides