title: Silibinin inhibits the invasion of IL-6-stimulated colon cancer cells via selective JNK/AP-1/MMP-2 modulation in vitro.
abstract: Silibinin is a flavonoid with antihepatotoxic properties and pleiotropic anticancer capabilities. This study investigated silibinin inhibition of cell invasion by down-regulating matrix metalloproteinase-2 (MMP-2) expression, via attenuation of activator protein-1 (AP-1) in IL-6-stimulated LoVo colon cancer cells. Western blot data showed that the expression of MMP-2 protein was reduced 1.6- or 1.7-fold over the control by treatment with silibinin or JNK inhibitor in the models. Similar results were revealed in zymography and confocal microscopy. Pretreatment with silibinin also abolished the binding activity of AP-1 and MMP-2 promoter activity via AP-1 binding, as observed by EMSA and luciferase assay. Finally, a [(3)H]-thymidine incorporation proliferation assay and cell migration assay demonstrated that silibinin inhibited IL-6-stimulated LoVo cell proliferation and invasion. Taken together, these data indicated that silibinin inhibits LoVo cell invasion with the reduction of MMP-2 presentation by attenuating AP-1 binding activity, suggesting a novel antimetastatic application for silibinin in colon cancer chemoprevention.
authors.affiliation: Department of Emergency Medicine,  Shin Kong Wu Ho-Su Memorial Hospital , Taipei, Taiwan.
authors.forename: Chiu-Mei
authors.initials: CM
authors.lastname: Lin
authors.forename: Yen-Hsu
authors.initials: YH
authors.lastname: Chen
authors.forename: Hon-Ping
authors.initials: HP
authors.lastname: Ma
authors.forename: Bao-Wei
authors.initials: BW
authors.lastname: Wang
authors.forename: Jen-Hwey
authors.initials: JH
authors.lastname: Chiu
authors.forename: Su-Kiat
authors.initials: SK
authors.lastname: Chua
authors.forename: Jiann-Ruey
authors.initials: JR
authors.lastname: Ong
authors.forename: Kou-Gi
authors.initials: KG
authors.lastname: Shyu
mesh_terms: D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D003110:Colonic Neoplasms / Q000473:pathology*; D006801:Humans; D015850:Interleukin-6 / Q000494:pharmacology; D048031:JNK Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors*; D048670:MAP Kinase Kinase 4; D020778:Matrix Metalloproteinase 2 / Q000032:analysis / Q000187:drug effects* / Q000235:genetics; D061965:Matrix Metalloproteinase Inhibitors / Q000494:pharmacology; D009361:Neoplasm Invasiveness / Q000517:prevention & control*; D011401:Promoter Regions, Genetic / Q000187:drug effects; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D000077385:Silybin; D012838:Silymarin / Q000494:pharmacology*; D018808:Transcription Factor AP-1 / Q000037:antagonists & inhibitors*
chemical_list: D015850:Interleukin-6; D061965:Matrix Metalloproteinase Inhibitors; D047428:Protein Kinase Inhibitors; D012838:Silymarin; D018808:Transcription Factor AP-1; D000077385:Silybin; D048031:JNK Mitogen-Activated Protein Kinases; D048670:MAP Kinase Kinase 4; D020778:Matrix Metalloproteinase 2