title: Melittin suppresses PMA-induced tumor cell invasion by inhibiting NF-kappaB and AP-1-dependent MMP-9 expression.
abstract: Matrix metalloproteinase-9 (MMP-9) plays an important role in the invasion and metastasis of cancer cells. In this study, we examined the inhibitory effect of bee venom (BV) and its major peptides, melittin and apamin, on PMA-induced invasion induced by MMP-9 expression in Caki-1 renal cancer cells. BV and melittin, but not apamin, significantly suppressed PMA-induced invasion by inhibiting MMP-9 expression in Caki-1 cells. Furthermore, as evidenced by MMP-9 promoter assays, melittin inhibited MMP-9 gene expression by blocking the PMA-stimulated activations of activator protein-1 (AP-1) and nuclear factor-kappa B (NF-kappaB). In addition, melittin suppressed the PMA-induced phosphorylations of ERK and JNK mitogen-activated protein kinases, upstream factors involved in Ap-1 and NF-kappaB. These results suggest that the suppression of MMP-9 expression contributes to the anti-tumor properties of melittin.
authors.affiliation: Department of Rehabilitation Medicine, Eulji University Hospital, Daejeon 302-799, Korea.
authors.forename: Jung Hyun
authors.initials: JH
authors.lastname: Park
authors.forename: Yun-Jeong
authors.initials: YJ
authors.lastname: Jeong
authors.forename: Kwan-Kyu
authors.initials: KK
authors.lastname: Park
authors.forename: Hyun-Ji
authors.initials: HJ
authors.lastname: Cho
authors.forename: Il-Kyung
authors.initials: IK
authors.lastname: Chung
authors.forename: Kwan-Sik
authors.initials: KS
authors.lastname: Min
authors.forename: Mihyun
authors.initials: M
authors.lastname: Kim
authors.forename: Kwang-Gill
authors.initials: KG
authors.lastname: Lee
authors.forename: Joo-Hong
authors.initials: JH
authors.lastname: Yeo
authors.forename: Kwang-Kyun
authors.initials: KK
authors.lastname: Park
authors.forename: Young-Chae
authors.initials: YC
authors.lastname: Chang
mesh_terms: D001030:Apamin / Q000494:pharmacology; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D004354:Drug Screening Assays, Antitumor; D004789:Enzyme Activation / Q000187:drug effects; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism; D020935:MAP Kinase Signaling System / Q000187:drug effects; D020780:Matrix Metalloproteinase 9 / Q000235:genetics / Q000378:metabolism*; D008555:Melitten / Q000494:pharmacology*; D016328:NF-kappa B / Q000378:metabolism*; D009361:Neoplasm Invasiveness / Q000473:pathology*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D013755:Tetradecanoylphorbol Acetate; D018808:Transcription Factor AP-1 / Q000378:metabolism*
chemical_list: D016328:NF-kappa B; D012333:RNA, Messenger; D018808:Transcription Factor AP-1; D008555:Melitten; D001030:Apamin; D048049:Extracellular Signal-Regulated MAP Kinases; D048031:JNK Mitogen-Activated Protein Kinases; D020780:Matrix Metalloproteinase 9; D013755:Tetradecanoylphorbol Acetate