Inhibition of matrix metalloproteinases related to metastasis by diosgenyl and pennogenyl saponins

Abstract

Ethnopharmacological relevanceDiosgenyl and pennogenyl saponins isolated from Rhizoma Paridis, showed pro-apoptosis and immunoregulation with antitumor activity in cultured cells and animal systems. Aim of the studyTo evaluate their anti-metastatic mechanism on cancer cells and discuss their structure-activity relationship on anti-tumor effect. Materials and methodsThis research used the wound healing and migration assay to detect their anti-invasive effect on B16 melanoma cells. Through the gelatin zymography assay, immunofluorescence analysis and western blot, saponins exhibited different levels of protein expression inhibition of MMP-1, -2, -3, -9 and -14. ResultsThrough the analysis, diosgenyl and pennogenyl saponins inhibited the metastasis of B16 melanoma cells. Diosgenyl saponins also showed strong suppression of enzyme activity of MMP-2 and -9. Different saponins exhibited different levels of inhibition on MMP expression. Conclusions17-α OH increases the sensitivity of diosgenyl saponins to the membrane-bound protease which can stimulate proMMP-2 activation, but it also decreases the anti-metastatic activity of diosgenyl saponin. Furthermore, their combination might provide a potential therapeutic modality for metastasis.