Modified apple polysaccharides suppress the migration and invasion of colorectal cancer cells induced by lipopolysaccharide.

Abstract

Metastasis is the major cause of death in colorectal cancer (CRC). In colitis-associated carcinogenesis, the activation of nuclear factor-κB (NF-κB) occurs via lipopolysaccharide (LPS) binding to the toll-like receptor 4 (TLR4). The LPS/TLR4/NF-κB pathway contributes to the development and metastasis of colitis-associated colon cancer. In the present study, we hypothesized that an extracted modified Fuji apple polysaccharide (MAP) would alter the LPS/TLR4/NF-κB pathway. Thus, we evaluated the effect of MAP in vitro on the LPS/TLR4/NF-κB pathway in CRC cells (HT-29 and SW620 cells). The results suggest that (i) MAP competed with LPS for binding to TLR4 to reduce LPS-induced NF-κB expression and (ii) MAP suppressed the nuclear translocation of NF-κB p65. MAP significantly decreased LPS-induced expression of TLR4, cyclooxygenase-2, matrix metallopeptidase 9 (MMP9), matrix metallopeptidase 2, inducible nitric oxide synthase, and prostaglandin E2, and it increased the protein expression of the inhibitor of κBα and NF-κB p65 in cytoplasm when it was given in combination with LPS. These results indicate that MAP suppressed LPS-induced migration and invasiveness of CRC cells by targeting the LPS/TLR4/NF-κB pathway. Therefore, we propose that MAP has potential for the clinical prevention of CRC cell metastasis.

• Authors: Dian Zhang, Yu-hua Li, Man Mi, Feng-Liang Jiang, Zheng-gang Yue, Yang Sun, Lei Fan, Jin Meng, Xin Zhang, Li Liu, Qi-Bing Mei
• Journal: Nutrition research (New York, N.Y.) (Nutr Res) Vol. 33 Issue 10 Pg. 839-48 (Oct 2013) ISSN: 1879-0739 [Electronic] United States
• PMID: 24074742 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2013 Elsevier Inc. All rights reserved.

Chemical References

• Anticarcinogenic Agents
• Antineoplastic Agents, Phytogenic
• I-kappa B Proteins
• Lipopolysaccharides
• NF-kappa B
• Plant Extracts
• Polysaccharides
• TLR4 protein, human
• Toll-Like Receptor 4
• Transcription Factor RelA
• NOS2 protein, human
• Nitric Oxide Synthase Type II
• MMP2 protein, human
• Matrix Metalloproteinase 2
• MMP9 protein, human
• Matrix Metalloproteinase 9
• Dinoprostone

Topics

• Anticarcinogenic Agents (pharmacology, therapeutic use)
• Antineoplastic Agents, Phytogenic (pharmacology, therapeutic use)
• Biological Transport (drug effects)
• Cell Movement (drug effects)
• Colitis (complications, metabolism, microbiology, pathology)
• Colon (metabolism, microbiology, pathology)
• Colorectal Neoplasms (etiology, metabolism, pathology, prevention & control)
• Dinoprostone (metabolism)
• Fruit (chemistry)
• HT29 Cells
• Humans
• I-kappa B Proteins (metabolism)
• Lipopolysaccharides (metabolism)
• Malus (chemistry)
• Matrix Metalloproteinase 2 (metabolism)
• Matrix Metalloproteinase 9 (metabolism)
• NF-kappa B (metabolism)
• Nitric Oxide Synthase Type II (metabolism)
• Phytotherapy
• Plant Extracts (pharmacology, therapeutic use)
• Polysaccharides (pharmacology, therapeutic use)
• Signal Transduction
• Toll-Like Receptor 4 (metabolism)
• Transcription Factor RelA (metabolism)