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.
Lee
Kyung Jin
KJ
BK21 Project Team, Department of Pharmacy, College of Pharmacy, Research Center for Proteinous Materials, Chosun University, Gwangju, South Korea.
Hwang
Soo Jin
SJ
Choi
Jae Ho
JH
Jeong
Hye Gwang
HG
D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D002465:Cell Movement / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D006801:Humans; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D061965:Matrix Metalloproteinase Inhibitors; D016328:NF-kappa B / Q000378:metabolism*; D009361:Neoplasm Invasiveness; D010936:Plant Extracts / Q000494:pharmacology*; D018517:Plant Roots / Q000737:chemistry; D031238:Platycodon; D017382:Reactive Oxygen Species / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000032:analysis
D000972:Antineoplastic Agents, Phytogenic; C440574:Changkil; D004791:Enzyme Inhibitors; D061965:Matrix Metalloproteinase Inhibitors; D016328:NF-kappa B; D010936:Plant Extracts; D017382:Reactive Oxygen Species; D019715:Tissue Inhibitor of Metalloproteinase-1; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9; D013755:Tetradecanoylphorbol Acetate