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.

Keywords: 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.