Inhibition of proinflammatory cytokine-induced invasiveness of HT-29 cells by chitosan oligosaccharide.
The effect of chitosan oligosaccharide (COS, 1 kDa <MW<3 kDa) on proinflammatory cytokines-induced nitric oxide (NO) production and invasiveness of human colorectal adenocarcinoma HT-29 cells was investigated. COS (0.1-5mg/ ml) suppressed the NO production induced by proinflammatory cytokines (100 U/ml IFN-gamma, 10 ng/ml IL-1alpha, and 25 ng/ml TNF-alpha) in HT-29 cells. Inducible nitric oxide synthase (iNOS) expression induced by these cytokines was inhibited by COS. COS pretreatment inhibited the invasiveness of cytokines-treated HT-29 cells through Matrigel-coated membrane in a dose-dependent manner. COS also inhibited cytokines-induced matrix metalloproteinase (MMP)-2 activity. This study shows that proinflammatory cytokines induce NO production, iNOS expression, and invasiveness of human colorectal adenocarcinoma HT-29 cells. COS pretreatment inhibited cytokines-mediated NO production, iNOS expression, and invasiveness of HT-29 cells. These results provide sufficient information for the further development of COS as an antitumor metastatic agent for the treatment of colon cancer.
Nam
Kyung-Soo
KS
Department of Pharmacology, College of Medicine, Dongguk University, Gyeongju 780-714, Korea.
Kim
Mee-Kyung
MK
Shon
Yun-Hee
YH
D000230:Adenocarcinoma / Q000188:drug therapy* / Q000201:enzymology / Q000276:immunology / Q000473:pathology; D015153:Blotting, Western; D002465:Cell Movement / Q000187:drug effects / Q000276:immunology; D048271:Chitosan / Q000494:pharmacology*; D003110:Colonic Neoplasms / Q000188:drug therapy* / Q000201:enzymology / Q000276:immunology / Q000473:pathology; D016207:Cytokines / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D004347:Drug Interactions; D004591:Electrophoresis, Polyacrylamide Gel; D019073:HT29 Cells; D006801:Humans; D007371:Interferon-gamma / Q000494:pharmacology; D053582:Interleukin-1alpha / Q000494:pharmacology; D008233:Lymphotoxin-alpha / Q000494:pharmacology; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D009361:Neoplasm Invasiveness; D052247:Nitric Oxide Synthase Type II / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D009570:Nitriles / Q000378:metabolism
D016207:Cytokines; D053582:Interleukin-1alpha; D008233:Lymphotoxin-alpha; D009570:Nitriles; D007371:Interferon-gamma; D048271:Chitosan; D052247:Nitric Oxide Synthase Type II; D020778:Matrix Metalloproteinase 2