title: Deoxypodophyllotoxin, flavolignan, from Anthriscus sylvestris Hoffm. inhibits migration and MMP-9 via MAPK pathways in TNF-alpha-induced HASMC.
abstract: The matrix metalloproteinases (MMP-9 and MMP-2) in aortic smooth muscle cells (SMC) play key roles in the pathogenesis atherosclerosis. The SMC migration into the vascular wall via the bloodstream is directly linked with MMP-9 expression. Deoxypodophyllotoxin (DPT), a naturally occurring flavolignan with anti-inflammatory activity, was isolated from Anthriscus sylvestris Hoffm. and has been known inhibit the expression of MMP-9 in tumor necrosis factor-alpha (TNF-alpha) stimulated human aortic smooth muscle cells (HASMC). In this study, DPT was purified and demonstrated to inhibit the MMP-9/2 activities in TNF-alpha-induced HASMC. In addition, MMP-9 expression and migration was strongly inhibited by DPT in TNF-alpha-induced HASMC. To examine whether TNF-alpha-induced MMP-9 expressions are involved with migrations of HASMC, reverse transcription-polymerase chain reaction (RT-PCR) and luciferase-tagged promoter analysis were applied. These experiments revealed that DPT inhibited the mRNA transcription of MMP-9 gene expression. Furthermore, Western blot analysis indicated that the TNF-alpha-induced phosphorylation of extracellular signal regulated kinase 1 and 2 (ERK1/2), p38 and c-Jun N-terminal kinase (JNK) were strongly inhibited by DPT. From these results, it is concluded that DPT has an inhibitory activities on migration and MMP-2/9 activities, and MMP-9 transcription in HASMC.
authors.affiliation: Department of Biological Science, Sungkyunkwan University, Chunchun-Dong 300, Jangan-Gu, Suwon City, Kyunggi-Do 440-746, Republic of Korea.
authors.forename: Seok-Jong
authors.initials: SJ
authors.lastname: Suh
authors.forename: Jeong-Ran
authors.initials: JR
authors.lastname: Kim
authors.forename: Un-Ho
authors.initials: UH
authors.lastname: Jin
authors.forename: Hong-Seo
authors.initials: HS
authors.lastname: Choi
authors.forename: Young-Chae
authors.initials: YC
authors.lastname: Chang
authors.forename: Young-Choon
authors.initials: YC
authors.lastname: Lee
authors.forename: Sung-Hoon
authors.initials: SH
authors.lastname: Kim
authors.forename: In-Seon
authors.initials: IS
authors.lastname: Lee
authors.forename: Tae Chul
authors.initials: TC
authors.lastname: Moon
authors.forename: Hyeun-Wook
authors.initials: HW
authors.lastname: Chang
authors.forename: Cheorl-Ho
authors.initials: CH
authors.lastname: Kim
mesh_terms: D001011:Aorta / Q000166:cytology / Q000187:drug effects / Q000201:enzymology*; D019661:Apiaceae / Q000737:chemistry / Q000502:physiology*; D002464:Cell Migration Inhibition / Q000187:drug effects* / Q000502:physiology; D002478:Cells, Cultured; D004365:Drugs, Chinese Herbal; D006801:Humans; D017705:Lignans / Q000302:isolation & purification / Q000494:pharmacology*; D020935:MAP Kinase Signaling System / Q000187:drug effects* / Q000502:physiology; D020780:Matrix Metalloproteinase 9 / Q000502:physiology; D061965:Matrix Metalloproteinase Inhibitors; D032389:Myocytes, Smooth Muscle / Q000166:cytology / Q000187:drug effects / Q000201:enzymology*; D010936:Plant Extracts / Q000302:isolation & purification / Q000494:pharmacology; D018517:Plant Roots; D011034:Podophyllotoxin / Q000031:analogs & derivatives* / Q000302:isolation & purification / Q000494:pharmacology; D011480:Protease Inhibitors / Q000302:isolation & purification / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000502:physiology
chemical_list: D004365:Drugs, Chinese Herbal; D017705:Lignans; D061965:Matrix Metalloproteinase Inhibitors; D010936:Plant Extracts; D011480:Protease Inhibitors; D014409:Tumor Necrosis Factor-alpha; C014451:deoxypodophyllotoxin; D020780:Matrix Metalloproteinase 9; D011034:Podophyllotoxin