The inhibitory mechanism of a novel cationic glucosamine derivative against MMP-2 and MMP-9 expressions

A number of recent researches have demonstrated the therapeutic effects of glucosamine (Glc) in a range of human diseases including arthritis. For the first time, we identified that a novel Glc derivative having quaternized amino functionality (QAGlc) suppresses MMP-9 and MMP-2, gelatinases in HT1080, human fibrosarcoma cells at 40 μg/ml, following stimulation with PMA. Reporter gene assay results revealed that, the mechanism of suppression involves decreased transcriptional activation of MMP-9 and MMP-2 via transcription factors NF-κB and AP-1. However based on western blot results, QAGlc did not attenuate the nuclear translocation of both NF-κB and AP-1. Apparently, phorbol myristate acetate (PMA) stimulated expressions of ERK, JNK and p38 were altered in the presence of potent tumour inducer, phorbol myristate acetate QAGlc, suggesting their suppression also contributes to QAGlc-mediated inhibition of MMP-9 and MMP-2. Moreover, the ability of QAGlc to inhibit gelatinases was confirmed by its ability to act against invasiveness of HT1080 cells through extracellular matrix components.

Graphical abstractNovel Glc derivative suppresses MMP-9 and MMP-2 in HT1080 cells by decreasing transcriptional activation of MMP-9 and MMP-2 via transcription factors NF-κB and AP-1. PMA-stimulated expressions of ERK, JNK and p38 were altered in the presence of QAGlc confirming its mechanism of inhibition.Figure optionsDownload full-size imageDownload as PowerPoint slide