Exp Mol Med.  2007 Jun;39(3):402-411.

Inhibition of trichostatin A-induced antiangiogenesis by small-interfering RNA for thrombospondin-1

• Kang JH
• Kim SA
• Chang SY
• Hong S
• Hong KJ

Abstract

Expression of thrombospondin-1 (TSP-1), which is a known inhibitor of tumor growth and angiogenesis, is reciprocally regulated by positive regulators, such as VEGF. Additionally, trichostatin A (TSA) suppresses tumor progression by altering VEGF levels and VEGF-mediated signaling. Thus, understanding TSA-regulated TSP-1 expression and the effects of altered TSP-1 levels might provide insights into the mechanism of action of TSA in anti-tumorigenesis, and provide an approach to cancer therapy. Here, we examined the effect of TSA on TSP-1 expression, and the effects of TSA-induced TSP-1 on cell motility and angiogenesis, in HeLa and bovine aortic endothelial cells. TSA remarkably increased TSP-1 expression at the mRNA and protein levels, by controlling the TSP-1 promoter activity. Both TSA and exogenous TSP-1 reduced cell migration and capillary-like tube formation and these activities were confirmed by blocking TSP-1 with its neutralizing antibody and small-interfering RNA. Our results suggest that TSP-1 is a potent mediator of TSA-induced anti- angiogenesis.

Keyword

angiogenesis; cell movement; histone deacetylases; RNA, small interfering; thrombospondin 1; trichostatin A

MeSH Terms

Angiogenesis Inhibitors/*pharmacology
Animals
Cattle
Cell Line
Cell Movement/*drug effects
Endothelial Cells/drug effects/*physiology
Humans
Hydroxamic Acids/*pharmacology
Neovascularization, Pathologic/metabolism/prevention & control
Neovascularization, Physiologic/*drug effects
RNA, Messenger/biosynthesis
RNA, Small Interfering/*genetics
Thrombospondin 1/*biosynthesis/genetics/pharmacology