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.

MATERIALS AND 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.

CONCLUSION:

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: Maria Stio, Maria Martinesi, Antonella Simoni, Ulrich Zuegel, Andreas Steinmeyer, Raffaella Santi, Cristina Treves, Gabriella Nesi
• Journal: Anticancer research (Anticancer Res) Vol. 31 Issue 12 Pg. 4091-8 (Dec 2011) ISSN: 1791-7530 [Electronic] Greece
• PMID: 22199266 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• ZK 191784
• Intercellular Adhesion Molecule-1
• Vitamin D
• Matrix Metalloproteinases
• Matrix Metalloproteinase 2
• Matrix Metalloproteinase 9
• Calcitriol

Topics

• Calcitriol (analogs & derivatives, pharmacology)
• Cell Line, Tumor
• Densitometry (methods)
• Humans
• Immunohistochemistry (methods)
• Intercellular Adhesion Molecule-1 (biosynthesis)
• Male
• Matrix Metalloproteinase 2 (biosynthesis)
• Matrix Metalloproteinase 9 (biosynthesis)
• Matrix Metalloproteinases (biosynthesis)
• Neoplasm Invasiveness
• Prostatic Neoplasms (metabolism)
• Vitamin D (analogs & derivatives)