Inhibition of trichostatin A-induced antiangiogenesis by small-interfering RNA for thrombospondin-1.
- Author:
Jung Hoon KANG
1
;
Soo A KIM
;
Seo Yoon CHANG
;
Susie HONG
;
Kyong Ja HONG
Author Information
1. Department of Physiology, College of Medicine, The Catholic University of Korea, Seoul 137-701, Korea.
- Publication Type:Original Article ; Research Support, Non-U.S. Gov't
- Keywords:
angiogenesis;
cell movement;
histone deacetylases;
RNA, small interfering;
thrombospondin 1;
trichostatin A
- MeSH:
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
- From:Experimental & Molecular Medicine
2007;39(3):402-411
- CountryRepublic of Korea
- Language:English
-
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.
