PRECLINICAL REPORTSDifferential regulation of thrombospondin-1 expression and antiangiogenesis of ECV304 cells by trichostatin A and helixor AHong, Susie; Chang, Seo-Yoon; Yeom, Dong-Hoon; Kang, Jung-Hoon; Hong, Kyong-JaAuthor Information Department of Biochemistry, College of Medicine, The Catholic University of Korea, Seoul, South Korea Correspondence to Professor Kyong-Ja Hong, PhD, Department of Biochemistry, College of Medicine, The Catholic University of Korea, 505 Banpo-dong Seocho-gu, Seoul 137-701, South Korea Tel: +82 2 590 1176; fax: +82 2 596 4435; e-mail: [email protected] Received 5 December 2006 Accepted 11 April 2007 Anti-Cancer Drugs: October 2007 - Volume 18 - Issue 9 - p 1005-1014 doi: 10.1097/CAD.0b013e3281e4429d Buy Metrics Abstract 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. © 2007 Lippincott Williams & Wilkins, Inc.