title: Saussurea lappa extract suppresses TPA-induced cell invasion via inhibition of NF-κB-dependent MMP-9 expression in MCF-7 breast cancer cells.
abstract: BACKGROUND
  Saussurea lappa (SL) has been used as a traditional herbal medicine to treat abdominal pain and tenesmus, and has been suggested to possess various biological activities, including anti-tumor, anti-ulcer, anti-inflammatory, anti-viral, and cardiotonic activities. The effect of SL on breast cancer metastasis, however, is unknown. Cell migration and invasion are crucial in neoplastic metastasis. Matrix metalloproteinase-9 (MMP-9), which degrades the extracellular matrix, is a major component in cancer cell invasion.
  
  
  METHODS
  Cell viability was examined by MTT assay, whereas cell motility was measured by invasion assay. Western blot, Real-time PCR, and Zymography assays were used to investigate the inhibitory effects of ESL on matrix metalloproteinase-9 (MMP-9) expression level in MCF-7 cells. EMSA confirmed the inhibitory effects of ESL on DNA binding of NF- κB in MCF-7 cells.
  
  
  RESULTS
  Cells threated with various concentrations of Saussurea lappa (ESL) for 24 h. Concentrations of 2 or 4 μM did not lead to a significant change in cell viability or morphology. Therefore, subsequent experiments utilized the optimal non-toxic concentration (2 or 4 μM) of ESL. In this study, we investigated the inhibitory effect of ethanol extract of ESL on MMP-9 expression and cell invasion in 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced MCF-7 cells. ESL inhibited the TPA-induced transcriptional activation of nuclear factor-kappa B (NF-κB). However, this result obtained that ESL did not block the TPA-induced phosphorylation of the kinases: p38, ERK, and JNK. Therefore, ELS-mediated inhibition of TPA-induced MMP-9 expression and cell invasion involves the suppression of NF-kB pathway in MCF-7 cells.
  
  
  CONCLUSIONS
  These results indicate that ELS-mediated inhibition of TPA-induced MMP-9 expression and cell invasion involves the suppression of NF-kB pathway in MCF-7 cells. Thus, ESL has potential for controlling breast cancer invasiveness in vitro.
authors.forename: Ha-Rim
authors.initials: HR
authors.lastname: Kim
authors.forename: Jeong-Mi
authors.initials: JM
authors.lastname: Kim
authors.forename: Mi-Seong
authors.initials: MS
authors.lastname: Kim
authors.forename: Jin-Ki
authors.initials: JK
authors.lastname: Hwang
authors.forename: Yeon-Ju
authors.initials: YJ
authors.lastname: Park
authors.forename: Sei-Hoon
authors.initials: SH
authors.lastname: Yang
authors.forename: Hye-Jung
authors.initials: HJ
authors.lastname: Kim
authors.forename: Do-Gon
authors.initials: DG
authors.lastname: Ryu
authors.forename: Dong-Sung
authors.initials: DS
authors.lastname: Lee
authors.forename: Hyuncheol
authors.initials: H
authors.lastname: Oh
authors.forename: Youn-Chul
authors.initials: YC
authors.lastname: Kim
authors.forename: Yun-Jin
authors.initials: YJ
authors.lastname: Rhee
authors.forename: Byung-Soon
authors.initials: BS
authors.lastname: Moon
authors.forename: Jong-Min
authors.initials: JM
authors.lastname: Yun
authors.affiliation: Center for Metabolic Function Regulation, Wonkwang University School of Medicine, Iksan 570-749, South Korea. desson@wku.ac.kr.
authors.forename: Kang-Beom
authors.initials: KB
authors.lastname: Kwon
authors.forename: Young-Rae
authors.initials: YR
authors.lastname: Lee
mesh_terms: D001943:Breast Neoplasms / Q000188:drug therapy / Q000201:enzymology* / Q000235:genetics / Q000473:pathology; D002465:Cell Movement / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D015536:Down-Regulation / Q000187:drug effects; D005260:Female; D006801:Humans; D061986:MCF-7 Cells; D020780:Matrix Metalloproteinase 9 / Q000235:genetics* / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism*; D009361:Neoplasm Invasiveness; D010766:Phosphorylation / Q000187:drug effects; D010936:Plant Extracts / Q000494:pharmacology*; D030441:Saussurea / Q000737:chemistry*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology*; D015533:Transcriptional Activation / Q000187:drug effects
chemical_list: D016328:NF-kappa B; D010936:Plant Extracts; D020780:Matrix Metalloproteinase 9; D013755:Tetradecanoylphorbol Acetate