Differential regulation of thrombospondin-1 expression and antiangiogenesis of ECV304 cells by trichostatin A and helixor A.
Trichostatin A and helixor A increased thrombospondin-1 expression by ECV304 cells at both mRNA and protein levels by transcriptional activation through the enhancement of tsp-1 promoter activity. The induction of thrombospondin-1 by these agents potently reduced ECV 304 cell migration and capillary-like tube formation on Matrigel; these findings were confirmed by the neutralization of thrombospondin-1 using a specific antibody. In the presence of exogenous vascular endothelial growth factor, however, these agents had a different effect on the vascular endothelial growth factor-induced tube formation; trichostatin A remarkably inhibited tube formation regardless of the presence of exogenous vascular endothelial growth factor, whereas helixor A reduced it to 70-80% of the control level. Interestingly, when the helixor A-generated conditioned media were concentrated three-fold and the endogenous vascular endothelial growth factor was removed, tube formation was remarkably inhibited compared with the effect of three-fold concentrated conditioned media that had endogenous vascular endothelial growth factor. Additionally, in media with endogenous vascular endothelial growth factor that were concentrated five-fold, tube formation was markedly blocked regardless of the presence of exogenous or endogenous vascular endothelial growth factor. Thus, our results indicate that trichostatin A-induced or helixor A-induced antiangiogenesis is mediated by both agents; increased, absolute and relative levels of thrombospondin-1 to the vascular endothelial growth factor level are critical in angiogenesis.
Hong
Susie
S
Department of Biochemistry, College of Medicine, The Catholic University of Korea, Seoul, South Korea.
Chang
Seo-Yoon
SY
Yeom
Dong-Hoon
DH
Kang
Jung-Hoon
JH
Hong
Kyong-Ja
KJ
D020533:Angiogenesis Inhibitors / Q000494:pharmacology*; D002460:Cell Line; D002465:Cell Movement / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D017077:Culture Media, Conditioned; D004305:Dose-Response Relationship, Drug; D042783:Endothelial Cells / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D006801:Humans; D006877:Hydroxamic Acids / Q000494:pharmacology*; D009389:Neovascularization, Pathologic / Q000378:metabolism / Q000517:prevention & control; D010936:Plant Extracts / Q000494:pharmacology*; D019700:Thrombospondin 1 / Q000096:biosynthesis* / Q000235:genetics; D015854:Up-Regulation; D042442:Vascular Endothelial Growth Factors / Q000494:pharmacology
D020533:Angiogenesis Inhibitors; D017077:Culture Media, Conditioned; D006877:Hydroxamic Acids; D010936:Plant Extracts; D019700:Thrombospondin 1; D042442:Vascular Endothelial Growth Factors; C012589:trichostatin A; C027633:Helixor