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 effect of curcumin on endothelial cell migration, attachment, and tube formation on Matrigel. Curcumin had no effect on endothelial cell migration or attachment to either plastic or Matrigel. Curcumin treatment resulted in a dose-dependent inhibition of tube formation when the cells were treated before plating or at the time of plating on Matrigel. Curcumin treatment also caused the preformed tubes to break down. Curcumin inhibited angiogenesis in a s.c. Matrigel plug model in mice. The role of metalloproteinases has been shown to be important in angiogenesis; therefore, zymography was performed to determine whether curcumin affected protease activity. Zymographs of curcumin-treated culture supernatants showed a decrease in the gelatinolytic activities of secreted 53- and 72-kDa metalloproteinases. Western and Northern analysis showed a dose-dependent decrease in the protein expression and transcript of 72 kDa, indicating that curcumin may be exerting its inhibitory effect at both the transcriptional and posttranscriptional level. These findings suggest that curcumin acts as an angiogenesis inhibitor by modulating protease activity during endothelial morphogenesis. Curcumin could be developed as an antiangiogenic drug.