Microarray-based Analysis of Anti-angiogenic Activity of Demethoxycurcumin on Human Umbilical Vein Endothelial Cells: Crucial Involvement of the Down-regulation of Matrix Metalloproteinase

cDNA microarray-based gene expression analysis has been successfully employed to explore the action mechanism and to validate the targets of several drugs. In the present study, we evaluated anti-angiogenic activity of demethoxycurcumin (DC), a structural analog of curcumin, isolated from Curcuma aromatica , and investigated the effect of DC on genetic reprogramming in cultured human umbilical vein endothelial cells (HUVECs) using cDNA microarray analysis. Of 1024 human cancer-focused genes arrayed, 187 genes were up-regulated and 72 genes were down-regulated at least 2-fold by DC. Interestingly, 9 angiogenesis-related genes were down-regulated over 5-fold in response to DC, suggesting that the genetic reprogramming was crucially involved in anti-angiogenesis by the compound. To verify the results obtained from cDNA microarray analysis, matrix metalloproteinase-9 (MMP-9), the product of one of the angiogenesis-related genes down-regulated over 5-fold by DC, was investigated using gelatin zymography. DC potently inhibited the expression of MMP-9, yet showed no direct effect on its activity. These data show that gene expressional change of MMP-9 is a major mediator for angiogenesis inhibition by DC. All genes identified and microarray data are available on the web at http://dasan.sejong.ac.kr/bioprobe/ .