Saponins derived from the roots of Platycodon grandiflorum inhibit HT-1080 cell invasion and MMPs activities: regulation of NF-kappaB activation via ROS signal pathway.

The chemopreventive effects of saponin derived from Platycodon grandiflorum (Changkil saponin; CKS) on tumor invasion and migration and the possible mechanisms involved in this protection were investigated in HT-1080 tumor cells. In this study, we found that CKS reduced 12-O-tetradecanoylphorbol-13-acetate (PMA)-enhanced Matrix metalloproteinases (MMP)-9 and MMP-2 activation in a dose-dependant manner and further inhibited HT-1080 cell invasion and migration. In addition, CKS suppressed PMA-enhanced expression of MMP-9 protein, mRNA and transcription activity levels through suppression of nuclear factor (NF)-kappaB activation without changing tissue inhibitor of metalloproteinase (TIMP)-1 level. CKS also reduced PMA-enhanced MMP-2 active forms through suppression of membrane-type 1 MMP (MT1-MMP) level, but did not alter MMP-2 and TIMP-2 levels. Moreover, reactive oxygen species (ROS) production induced by PMA was partly decreased in the presence of CKS and this suppression of ROS production may be related to diminish NF-kappaB activity. Therefore, our results suggested that the inhibitory effects of CKS on MMP-2 and MMP-9 activation, relation of tumor invasion and migration in vitro possibly involve mechanisms related to its ability to suppress PMA-enhanced NF-kappaB activation through ROS signaling pathway. Overall, CKS may be a valuable anti-invasive drug candidate for cancer therapy.