INHIBITION OF ANGIOGENIC DIFFERENTIATION OF HUMAN UMBILICAL VEIN ENDOTHELIAL-CELLS BY CURCUMIN

Angiogenesis is a crucial step in the growth and metastasis of cancers , Curcumin inhibits tumor initiation and growth. We analyzed the effec t of curcumin on endothelial cell migration, attachment, and tube form ation on Matrigel. Curcumin had no effect on endothelial cell migratio n or attachment to either plastic or Matrigel. Curcumin treatment resu lted in a dose-dependent inhibition of tube formation when the cells w ere treated before plating or at the time of plating on Matrigel. Curc umin treatment also caused the preformed tubes to break down. Curcumin inhibited angiogenesis in a s.c. Matrigel plug model in mice, The rol e of metalloproteinases has been shown to be important in angiogenesis ; therefore, zymography was performed to determine whether curcumin af fected protease activity. Zymographs of curcumin-treated culture super natants showed a decrease in the gelatinolytic activities of secreted 53- and 72-kDa metalloproteinases. Western and Northern analysis showe d a dose-dependent decrease in the protein expression and transcript o f 72 kDa, indicating that curcumin may be exerting its inhibitory effe ct at both the transcriptional and posttranscriptional level. These fi ndings suggest that curcumin acts as an angiogenesis inhibitor by modu lating protease activity during endothelial morphogenesis. Curcumin co uld be developed as an antiangiogenic drug.