title: An apple oligogalactan suppresses endotoxin-induced cyclooxygenase-2 expression by inhibition of LPS pathways.
abstract: Colorectal cancer (CRC) is one of the most common cancers and a leading cause of cancer-related mortality in developed countries. Many ingredients of apples have been proven to have anti-inflammatory and anti-carcinogenic characteristics, and show benefits for CRC prevention. The aim of this study, therefore, was to evaluate inhibitory effect of an apple oligogalactan (AOG) on pro-inflammatory endotoxin lipopolysaccharide (LPS)-activated human colon carcinoma cells HT-29 and SW-620 and investigate the possible mechanisms. The two cell lines were pretreated with AOG (0.1-1 g/L) for 30 min and then treated with 10 μg/mL LPS. Real time PCR, Western blot, electrophoretic mobility shift assay (EMSA), and ELISA were used to detect the expression and activity of cyclooxygenase-2 (COX-2), NF-κB and MAPKs pathways. AOG significantly inhibited the expression and activity of COX-2 in LPS-activated human colon carcinoma cells HT-29 and SW-620. The mechanisms of AOG-suppressed COX-2 expression may be through inhibiting the phosphorylation of MAPKs and the activation of NF-κB and AP-1. These data may provide another molecular basis for understanding how apples act to prevent CRC and indicate that AOG may be useful for treatment of colitis and prevention of carcinogenesis.
authors.affiliation: Key Laboratory of Gastrointestinal Pharmacology of Chinese Materia Medica of the State Administration of Traditional Chinese Medicine, Collaborative Innovation Center for Chinese Medicine in Qinba Mountains, Department of Pharmacology, School of Pharmacy, Fourth Military Medical University, Xi'an 710032, Shaanxi, PR China; Department of Oncology, Xijing Hospital, Fourth Military Medical University, Xi'an 710032, Shaanxi, PR China.
authors.forename: Yuhua
authors.initials: Y
authors.lastname: Li
authors.forename: Lei
authors.initials: L
authors.lastname: Fan
authors.forename: Yang
authors.initials: Y
authors.lastname: Sun
authors.forename: Dian
authors.initials: D
authors.lastname: Zhang
authors.forename: Zhenggang
authors.initials: Z
authors.lastname: Yue
authors.forename: Yinbo
authors.initials: Y
authors.lastname: Niu
authors.forename: Jin
authors.initials: J
authors.lastname: Meng
authors.forename: Tiehong
authors.initials: T
authors.lastname: Yang
authors.forename: Wenchao
authors.initials: W
authors.lastname: Liu
authors.forename: Qibing
authors.initials: Q
authors.lastname: Mei
mesh_terms: D045744:Cell Line, Tumor; D051546:Cyclooxygenase 2 / Q000235:genetics*; D004789:Enzyme Activation / Q000187:drug effects; D005685:Galactans / Q000494:pharmacology*; D005786:Gene Expression Regulation / Q000187:drug effects*; D019073:HT29 Cells; D006801:Humans; D008070:Lipopolysaccharides / Q000378:metabolism* / Q000494:pharmacology; D027845:Malus / Q000737:chemistry*; D020928:Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors; D016328:NF-kappa B / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects*; D018808:Transcription Factor AP-1 / Q000378:metabolism
chemical_list: D005685:Galactans; D008070:Lipopolysaccharides; D016328:NF-kappa B; D018808:Transcription Factor AP-1; D051546:Cyclooxygenase 2; D020928:Mitogen-Activated Protein Kinases
keywords: An apple oligogalactan (AOG); Cyclooxygenase-2 (COX-2); Lipopolysaccharide (LPS)