Pro-angiogenesis action of arsenic and its reversal by selenium-derived compounds.

Abstract

Inorganic arsenic (arsenite and arsenate) in drinking water has been associated with skin cancers and increased incidence of cardiovascular diseases. Additionally, studies have demonstrated the pro-angiogenic effect of arsenite and its potential promotion of tumor angiogenesis and tumor progression. Furthermore, recent reports demonstrated reversal of skin co-carcinogenesis by an organoselenium compound. The present study was undertaken to determine the effect and mechanism on angiogenesis of arsenite at low level and its potential reversal by various selenium-derived compounds. The pro-angiogenesis effects and mechanisms of sodium arsenite were determined using the chick chorioallantoic membrane (CAM) model over 3 days and compared with standard pro-angiogenesis factors, such as basic fibroblast growth factor (b-FGF). Additionally, the potential effect of various selenium-derived compounds--such as dimethyl selenone, diphenyl selenone, sodium selenite or Se-methyl selenocysteine--in reversing the pro-angiogenesis effect of arsenite or b-FGF was also determined in the CAM model. The pro-angiogenesis effect of arsenite or b-FGF was significantly (P < 0.01) blocked by dimethyl selenone, diphenyl selenone, sodium selenite or Se-methyl selenocysteine. The pro-angiogenesis effect of either sodium arsenite at 33 nM or b-FGF was blocked (P < 0.01) by the extracellular signal-regulated kinases 1 and 2 (ERK1/2) activation inhibitor, PD 98059. Additionally, the pro-angiogenic effect of arsenic or b-FGF was blocked as well (P < 0.01) by the alphavbeta3 antagonist, XT199. These data suggest that the pro-angiogenesis effect of arsenic is initiated at the plasma membrane integrin alphavbeta3, involves activation of the ERK1/2 pathway and is effectively reversed by various selenium-derived compounds.

• Authors: Shaker A Mousa, Laura O'Connor, Toby G Rossman, Eric Block
• Journal: Carcinogenesis (Carcinogenesis) Vol. 28 Issue 5 Pg. 962-7 (May 2007) ISSN: 0143-3334 [Print] England
• PMID: 17158527 (Publication Type: Comparative Study, Journal Article, Research Support, U.S. Gov't, Non-P.H.S.)

Chemical References

• 3-(3-(3-(4,5-dihydroimidazol-2-ylamino)propyloxylisoxazol-5-yl)carbonylamino)-2-(phenylsulfonylamino)propionic acid
• Angiogenesis Inducing Agents
• Arsenites
• Flavonoids
• Imidazoles
• Selenium Compounds
• Sodium Compounds
• Fibroblast Growth Factor 2
• sodium arsenite
• Mitogen-Activated Protein Kinase 3
• 2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one

Topics

• Angiogenesis Inducing Agents (pharmacology)
• Animals
• Arsenites (antagonists & inhibitors, pharmacology)
• Chick Embryo
• Chorioallantoic Membrane (blood supply, drug effects)
• Fibroblast Growth Factor 2 (pharmacology)
• Flavonoids (pharmacology)
• Imidazoles (pharmacology)
• Mitogen-Activated Protein Kinase 3 (antagonists & inhibitors)
• Neovascularization, Pathologic (chemically induced)
• Selenium Compounds (pharmacology)
• Sodium Compounds (antagonists & inhibitors, pharmacology)