Abstract
We have studied the effect of curcumin (diferuloylmethane), a major component of the food flavor turmeric, on the proliferation and cell cycle progression of human umbilical vein endothelial cells (HUVEC). Curcumin inhibited the DNA synthesis of HUVEC as revealed by [3H]thymidine incorporation in a dose-dependent manner without significantly affecting the viability of the cells. The growth of HUVEC stimulated with fibroblast growth factor (FGF) and endothelial growth supplement (ECGS) was also inhibited by curcumin. Addition of curcumin to HUVEC resulted in an accumulation of > 46% of the cells in early S-phase, as determined by the FACS analysis. Pulse labeling studies with [3H]thymidine demonstrated that curcumin affected cells that were actively undergoing DNA synthesis. The de-novo synthesis of thymidine depends on thymidine kinase (TK) enzyme. Curcumin caused a significant loss of TK activity, which may be one of the possible mechanism(s) for the inhibition of DNA synthesis activity of HUVEC by curcumin. These studies have revealed a unique mode of action of curcumin whereby it effectively blocked the cell cycle progression during S-phase by inhibiting the activity of TK enzyme. The migration, proliferation and differentiation of HUVEC leads to angiogenesis, which facilitates the tumor initiation and promotion. Since curcumin inhibited the proliferation of HUVEC, it could turn out to be a very useful compound for the development of novel anti-cancer therapy.
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