title: Doxycycline down-regulates matrix metalloproteinase expression and inhibits NF-κB signaling in LPS-induced PC3 cells.
abstract: BACKGROUND
  Matrix metalloproteinase enzymes (MMPs) play important role in inflammation, malignant cell proliferation, invasion and angiogenesis by mediating extracellular matrix degradation. Doxycycline, a synthetic tetracycline, behaves as a MMP inhibitor at a subantimicrobial dose and inhibits tumor cell proliferation, invasion and angiogenesis. The aberrant activity of nuclear factor kappa B (NF-κB) causes activation of MMPs and thereby proliferation and invasion of cancer cells. The aim of this study was to investigate the effects of doxycycline on the expression of MMPs in lipopolysaccharide (LPS)-induced PC3 human prostate cancer cells and the possible role of NF-κB signaling.
  
  
  METHODS
  PC3 cells were incubated with LPS (0.5 μg/mL) for 24 h in the presence or absence of doxycycline (5 μg/mL). The effects of LPS and doxycycline on the expressions of MMP-2, MMP-8, MMP-9, MMP-10, NF-κB/p65, IκB-α, p-IκB-α, IKK-β were examined by Western blotting and immunohistochemistry in PC3 cells. Furthermore, relative proteinase activities of MMP-2 and MMP-9 were determined by gelatin zymography.
  
  
  RESULTS
  LPS increased expression and activity of MMP-9 and expression of MMP-8, MMP-10, NF-κB /p65, p-IκB-α, IKK-β and doxycycline down-regulated its effects with the exception of MMP-10 expression. The expression of MMP-2 and IκB-α was affected by neither LPS nor doxycycline.
  
  
  CONCLUSIONS
  Our findings indicate that doxycycline inhibits the expression of various MMPs and NF-κB signaling may play a role in the regulation of MMPs expression in LPS-induced PC3 human prostate cancer cells.
authors.forename: Deniz
authors.initials: D
authors.lastname: Ogut
authors.affiliation: Department of Pharmacology, Faculty of Pharmacy, Ege University, Bornova-Izmir. buket.reel@ege.edu.tr.
authors.forename: Buket
authors.initials: B
authors.lastname: Reel
authors.forename: Ceren
authors.initials: C
authors.lastname: Gonen Korkmaz
authors.forename: Mehmet Zuhuri
authors.initials: MZ
authors.lastname: Arun
authors.forename: Serap
authors.initials: S
authors.lastname: Cilaker Micili
authors.forename: Bekir Ugur
authors.initials: BU
authors.lastname: Ergur
mesh_terms: D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D015536:Down-Regulation / Q000187:drug effects; D004318:Doxycycline / Q000494:pharmacology*; D004789:Enzyme Activation; D018093:Gelatinases / Q000378:metabolism; D006801:Humans; D051550:I-kappa B Kinase / Q000378:metabolism; D007150:Immunohistochemistry; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008297:Male; D020782:Matrix Metalloproteinases / Q000096:biosynthesis*; D000072000:NF-KappaB Inhibitor alpha / Q000378:metabolism; D016328:NF-kappa B / Q000037:antagonists & inhibitors* / Q000378:metabolism; D009361:Neoplasm Invasiveness; D011471:Prostatic Neoplasms / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D015398:Signal Transduction / Q000187:drug effects; D051996:Transcription Factor RelA / Q000378:metabolism
chemical_list: D008070:Lipopolysaccharides; D016328:NF-kappa B; D051996:Transcription Factor RelA; D000072000:NF-KappaB Inhibitor alpha; D051550:I-kappa B Kinase; C496560:IKBKB protein, human; D018093:Gelatinases; D020782:Matrix Metalloproteinases; D004318:Doxycycline
keywords: MMPs; NF-kB; PC3 cells; Western blotting; doxycycline; immunohistochemistry; prostate cancer; zymography