title: The novel vitamin D analog ZK191784 inhibits prostate cancer cell invasion.
abstract: BACKGROUND
  Low serum levels of 1,25(OH)(2)D(3) (1,25D), have been associated with aggressive biologic behavior of prostate cancer (PCa). In the present study, we examined the effects of 1,25D and its novel, low-calcemic analog ZK191784 (ZK) on matrix metalloproteinases (MMPs), as well as on intercellular adhesion molecule-1 (ICAM-1) protein levels in human PCa cell lines LNCaP and DU-145.
  
  
  METHODS
  Cells were incubated with either vehicle (control), 1,25D or ZK. MMP-2 and MMP-9 activity was determined by gelatin zymography, while ICAM-1 levels were assessed by Western blot analysis and immunocytochemistry.
  
  
  RESULTS
  Compared to the controls, 1,25D and ZK caused a marked dose-dependent decrease in the gelatinolytic activity of the MMPs under study, particularly when ZK was used. Likewise, ICAM-1 was down-regulated in the cells incubated with 1,25D or ZK.
  
  
  CONCLUSIONS
  Vitamin D analogs appear to be involved in the regulation of extracellular MMP activity and membrane adhesion molecule expression. Further studies, both in vitro and in vivo, are needed to define their role as potential therapeutic tools.
authors.affiliation: Department of Biochemical Sciences, University of Florence, Florence, Italy.
authors.forename: Maria
authors.initials: M
authors.lastname: Stio
authors.forename: Maria
authors.initials: M
authors.lastname: Martinesi
authors.forename: Antonella
authors.initials: A
authors.lastname: Simoni
authors.forename: Ulrich
authors.initials: U
authors.lastname: Zuegel
authors.forename: Andreas
authors.initials: A
authors.lastname: Steinmeyer
authors.forename: Raffaella
authors.initials: R
authors.lastname: Santi
authors.forename: Cristina
authors.initials: C
authors.lastname: Treves
authors.forename: Gabriella
authors.initials: G
authors.lastname: Nesi
mesh_terms: D002117:Calcitriol / Q000031:analogs & derivatives* / Q000494:pharmacology; D045744:Cell Line, Tumor; D003720:Densitometry / Q000379:methods; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D018799:Intercellular Adhesion Molecule-1 / Q000096:biosynthesis; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000096:biosynthesis; D020780:Matrix Metalloproteinase 9 / Q000096:biosynthesis; D020782:Matrix Metalloproteinases / Q000096:biosynthesis; D009361:Neoplasm Invasiveness; D011471:Prostatic Neoplasms / Q000378:metabolism*; D014807:Vitamin D / Q000031:analogs & derivatives*
chemical_list: C470666:ZK 191784; D018799:Intercellular Adhesion Molecule-1; D014807:Vitamin D; D020782:Matrix Metalloproteinases; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9; D002117:Calcitriol