title: 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.
abstract: 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.
authors.affiliation: BK21 Project Team, Department of Pharmacy, College of Pharmacy, Research Center for Proteinous Materials, Chosun University, Gwangju, South Korea.
authors.forename: Kyung Jin
authors.initials: KJ
authors.lastname: Lee
authors.forename: Soo Jin
authors.initials: SJ
authors.lastname: Hwang
authors.forename: Jae Ho
authors.initials: JH
authors.lastname: Choi
authors.forename: Hye Gwang
authors.initials: HG
authors.lastname: Jeong
mesh_terms: 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
chemical_list: 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