Inhibition of trichostatin A-induced antiangiogenesis by small-interfering RNA for thrombospondin-1.
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.
Kang
Jung Hoon
JH
Department of Physiology, College of Medicine, The Catholic University of Korea, Seoul 137-701, Korea.
Kim
Soo-A
SA
Chang
Seo-Yoon
SY
Hong
Susie
S
Hong
Kyong-Ja
KJ
D020533:Angiogenesis Inhibitors / Q000494:pharmacology*; D000818:Animals; D002417:Cattle; D002460:Cell Line; D002465:Cell Movement / Q000187:drug effects*; D042783:Endothelial Cells / Q000187:drug effects / Q000502:physiology*; D006801:Humans; D006877:Hydroxamic Acids / Q000494:pharmacology*; D009389:Neovascularization, Pathologic / Q000378:metabolism / Q000517:prevention & control; D018919:Neovascularization, Physiologic / Q000187:drug effects*; D012333:RNA, Messenger / Q000096:biosynthesis; D034741:RNA, Small Interfering / Q000235:genetics*; D019700:Thrombospondin 1 / Q000096:biosynthesis* / Q000235:genetics / Q000494:pharmacology
D020533:Angiogenesis Inhibitors; D006877:Hydroxamic Acids; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D019700:Thrombospondin 1; C012589:trichostatin A