Modified apple polysaccharides suppress the migration and invasion of colorectal cancer cells induced by lipopolysaccharide.
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.
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; Department of Pathogen Biology and Immunology, Xi'an Medical University, Xi'an, China.
Dian
D
Zhang
Yu-hua
YH
Li
Man
M
Mi
Feng-Liang
FL
Jiang
Zheng-gang
ZG
Yue
Yang
Y
Sun
Lei
L
Fan
Jin
J
Meng
Xin
X
Zhang
Li
L
Liu
Qi-Bing
QB
Mei
D016588:Anticarcinogenic Agents / Q000494:pharmacology / Q000627:therapeutic use; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology / Q000627:therapeutic use; D001692:Biological Transport / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects; D003092:Colitis / Q000150:complications* / Q000378:metabolism / Q000382:microbiology / Q000473:pathology; D003106:Colon / Q000378:metabolism / Q000382:microbiology / Q000473:pathology*; D015179:Colorectal Neoplasms / Q000209:etiology / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D015232:Dinoprostone / Q000378:metabolism; D005638:Fruit / Q000737:chemistry; D019073:HT29 Cells; D006801:Humans; D020672:I-kappa B Proteins / Q000378:metabolism; D008070:Lipopolysaccharides / Q000378:metabolism*; D027845:Malus / Q000737:chemistry*; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D008517:Phytotherapy; D010936:Plant Extracts / Q000494:pharmacology / Q000627:therapeutic use; D011134:Polysaccharides / Q000494:pharmacology / Q000627:therapeutic use*; D015398:Signal Transduction; D051197:Toll-Like Receptor 4 / Q000378:metabolism; D051996:Transcription Factor RelA / Q000378:metabolism
D016588:Anticarcinogenic Agents; D000972:Antineoplastic Agents, Phytogenic; D020672:I-kappa B Proteins; D008070:Lipopolysaccharides; D016328:NF-kappa B; D010936:Plant Extracts; D011134:Polysaccharides; C495345:TLR4 protein, human; D051197:Toll-Like Receptor 4; D051996:Transcription Factor RelA; C496319:NOS2 protein, human; D052247:Nitric Oxide Synthase Type II; C522361:MMP2 protein, human; D020778:Matrix Metalloproteinase 2; C579270:MMP9 protein, human; D020780:Matrix Metalloproteinase 9; D015232:Dinoprostone
AP; Apple polysaccharides; COX2; CRC; Colorectal cancer; ELISA; FBS; FITC; IκBα; LPS; Lipopolysaccharide; MAP; MMP; MMP2; MMP9; NF-κB; PBS; PGE2; TLR4; apple polysaccharide; colorectal cancer; cyclooxygenase-2; enzyme-linked immunosorbent assay; fetal bovine serum; fluorescein isothiocyanate; iNOS; inducible nitric oxide synthase; inhibitor of κBα; lipopolysaccharide; matrix metallopeptidase; modified apple polysaccharide; nuclear factor-κB; phosphate-buffered saline; prostaglandin E2; toll-like receptor 4