Carboxymethylations of chitosan and chitin inhibit MMP expression and ROS scavenging in human fibrosarcoma cells

Abstract

The water-soluble derivatives of chitosan and chitin, carboxymethyl-chitosan (CM-chitosan) and carboxymethyl-chitin (CM-chitin), were synthesised by means of carboxymethylation reaction. Their antioxidative and matrix metalloproteinase-2 and -9 (MMP-2 and -9) inhibitory effects were investigated in HT1080 human fibrosarcoma cells. Treatment with CM-chitosan and CM-chitin suppressed the formation of intracellular reactive oxygen species (ROS), protein oxidation and lipid peroxidation in a concentration-dependent manner. In addition, a protective effect against oxidative damage of purified genomic DNA was observed in the presence of CM-chitosan and CM-chitin. Moreover, CM-chitosan and CM-chitin reduced the expression levels of MMP-2 and -9 in gelatin zymography, RT-PCR and western blot analysis without any cytotoxic influence. CM-chitin exhibited a higher MMP inhibitory effect than CM-chitosan through transcriptional down-regulations of activator protein-1 (AP-1) and nuclear factor κB (NF-κB). Findings from the present study underscore the nutraceutical value of CM-chitosan and CM-chitin as a potent antioxidant and MMP inhibitor via alleviations of radical-induced oxidative damage.