Modulation of
pathological angiogenesis by
curcumin (
diferuloylmethane), the active principle of turmeric, seems to be an important possibility meriting mechanistic investigations. In this report, we have studied the effect of
curcumin on the growth of
Ehrlich ascites tumor cells and endothelial cells in vitro. Further, regulation of
tumor angiogenesis by modulation of angiogenic
ligands and their receptor gene expression in
tumor and endothelial cells, respectively, by
curcumin was investigated.
Curcumin, when injected intraperitoneally (i.p) into mice, effectively decreased the formation of
ascites fluid by 66% in EAT bearing mice in vivo. Reduction in the number of EAT cells and human umbelical vein endothelial cells (HUVECs) in vitro by
curcumin, without being cytotoxic to these cells, is attributed to induction of apoptosis by
curcumin, as is evident by an increase in cells with fractional
DNA content seen in our results on FACS analysis. However,
curcumin had no effect on the growth of NIH3T3 cells.
Curcumin proved to be a potent angioinhibitory compound, as demonstrated by inhibition of angiogenesis in two in vivo angiogenesis assay systems, viz. peritoneal angiogenesis and chorioallantoic membrane assay. The angioinhibitory effect of
curcumin in vivo was corroborated by the results on down-regulation of the expression of proangiogenic genes, in EAT, NIH3T3, and endothelial cells by
curcumin. Our results on Northern blot analysis clearly indicated a time-dependent (0-24h) inhibition by
curcumin of
VEGF,
angiopoietin 1 and 2 gene expression in EAT cells,
VEGF and
angiopoietin 1 gene expression in NIH3T3 cells, and KDR gene expression in HUVECs. Further, decreased
VEGF levels in
conditioned media from cells treated with various doses of
curcumin (1 microM-1mM) for various time periods (0-24h) confirm its angioinhibitory action at the level of gene expression. Because of its non-toxic nature,
curcumin could be further developed to treat
chronic diseases that are associated with extensive neovascularization.