C₆₀(OH)₂₂: a potential histone deacetylase inhibitor with anti-angiogenic activity

C₆₀(OH)₂₂ has been reported to suppress human cancer by inhibiting angiogenesis. However, its mechanism of action remains unclear. To explore the role and mechanism of C₆₀(OH)₂₂ in human pancreatic cancer, siRNA knockdown, immunofluorescence and a matrigel plug mouse model were employed. The results demonstrated that C₆₀(OH)₂₂ suppresses endothelial cell invasion and tube formation in vitro. C₆₀(OH)₂₂ suppresses angiogenesis in human umbilical vein endothelial cell (HUVEC) xenograft mice. The enzymatic activities of MMP2 and MMP9, as well as the expression levels of HDAC1, HDAC2, HIF-1α and VEGF, were inhibited by C₆₀(OH)₂₂. The expression of RECK was up-regulated by C₆₀(OH)₂₂ in HUVECs. The expression levels of HIF-1α and VEGF were down-regulated and the expression of RECK was up-regulated after the knockdown of HDAC1 and HDAC2 in HUVECs. Cell invasion, tube formation, and the enzymatic activities of MMP2 and MMP9 were suppressed after the knockdown of HDAC1 or HDAC2 in HUVECs.