title: Celastrol inhibits breast cancer cell invasion via suppression of NF-ĸB-mediated matrix metalloproteinase-9 expression.
abstract: OBJECTIVE
  Metastasis is one of the main causes of death for patients with malignant tumors. Induction of matrix metalloproteinase (MMP)-9 is particularly important for the invasiveness of various cancer cells. Celastrol, a triterpenoid isolated from the traditional Chinese medicine, is known to inhibit the proliferation of a variety of tumor cells, including leukemia, glioma, prostate and breast cancer cells. In this study, we investigated the effect of celastrol on the migration and invasion of human breast carcinoma cells.
  
  
  RESULTS
  We observed that celastrol suppressed phorbol 12-myristate 13-acetate (PMA)-induced invasion and migration of MCF-7 cells. We also found that celastrol inhibited PMA-induced MMP-9 expression at both the mRNA and the protein levels, and the proteolytic activity of MMP-9 in MCF-7 cells. Our results revealed that celastrol inhibited the transcriptional activity of MMP-9 by suppression of the DNA binding activity of NF-κB in the MMP-9 promoter, and inhibited degradation of IκBα and nuclear translocation of NF-κB.
  
  
  CONCLUSIONS
  These results indicate that celastrol inhibits NF-κB-mediated MMP-9 expression, resulting in suppression of breast cancer cell invasion and migration that is induced by PMA. Celastrol is a potential agent for clinical use in preventing the invasion and metastasis of human malignant breast tumors.
authors.affiliation: School of Life Sciences and Biotechnology, Korea University, Seoul, Korea.
authors.forename: Yoonseo
authors.initials: Y
authors.lastname: Kim
authors.forename: Hyereen
authors.initials: H
authors.lastname: Kang
authors.forename: Sung-Wuk
authors.initials: SW
authors.lastname: Jang
authors.forename: Jesang
authors.initials: J
authors.lastname: Ko
mesh_terms: D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D001943:Breast Neoplasms / Q000378:metabolism / Q000473:pathology; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D005260:Female; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects*; D006801:Humans; D051550:I-kappa B Kinase / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000235:genetics / Q000378:metabolism; D061965:Matrix Metalloproteinase Inhibitors; D008516:Medicine, Chinese Traditional; D016328:NF-kappa B / Q000378:metabolism*; D009361:Neoplasm Invasiveness; D053978:Pentacyclic Triterpenes; D011401:Promoter Regions, Genetic; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014315:Triterpenes / Q000494:pharmacology*
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D061965:Matrix Metalloproteinase Inhibitors; D016328:NF-kappa B; D053978:Pentacyclic Triterpenes; D014315:Triterpenes; D051550:I-kappa B Kinase; D020780:Matrix Metalloproteinase 9; C050414:celastrol; D013755:Tetradecanoylphorbol Acetate