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KMID : 0620920070390030402
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Experimental & Molecular Medicine
2007 Volume.39 No. 3 p.402 ~ p.411
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Inhibition of trichostatin A-induced antiangiogenesis by small-interfering RNA for thrombospondin-1
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Kang Jung-Hoon
Kim Soo-A
Chang Seo-Yoon
Hong Su-Sie
Hong Kyong-Ja
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Abstract
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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.
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KEYWORD
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angiogenesis, cell movement, histone deacetylases, RNA, small interfering, thrombospondin 1, trichostatin A
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