Abstract
BackroundCurcumin from turmeric is an ingredient in curry powders. Due to its antiinflammatory, antioxidant and anticarcinogenic effects, curcumin is a promising drug for the treatment of cancer and retinal diseases. We investigated whether curcumin alters the viability and physiological properties of human retinal pigment epithelial (RPE) cells in vitro.Methodology/Principal FindingsCellular proliferation was investigated with a bromodeoxy-uridine immunoassay, and chemotaxis was investigated with a Boyden chamber assay. Cell viability was determined by trypan blue exclusion. Apoptosis and necrosis rates were determined with a DNA fragmentation ELISA. Gene expression was determined by real-time PCR, and secretion of VEGF and bFGF was examined with ELISA. The phosphorylation level of proteins was revealed by Western blotting. The proliferation of RPE cells was slightly increased by curcumin at 10 µM and strongly reduced by curcumin above 50 µM. Curcumin at 50 µM increased slightly the chemotaxis of the cells. Curcumin reduced the expression and secretion of VEGF under control conditions and abolished the VEGF secretion induced by PDGF and chemical hypoxia. Whereas low concentrations of curcumin stimulated the expression of bFGF and HGF, high concentrations caused downregulation of both factors. Curcumin decreased dose-dependently the viability of RPE cells via induction of early necrosis (above 10 µM) and delayed apoptosis (above 1 µM). The cytotoxic effect of curcumin involved activation of caspase-3 and calpain, intracellular calcium signaling, mitochondrial permeability, oxidative stress, increased phosphorylation of p38 MAPK and decreased phosphorylation of Akt protein.ConclusionIt is concluded that curcumin at concentrations described to be effective in the treatment of tumor cells and in inhibiting death of retinal neurons (∼10 µM) has adverse effects on RPE cells. It is suggested that, during the intake of curcumin as concomitant therapy of cancer or in the treatment of eye diseases, retinal function should be monitored carefully.
Highlights
The natural phenolic compound curcumin, the yellow pigment of turmeric and an ingredient in curry powders, has a long history of use in traditional Asian medicine for a wide variety of disorders
It is concluded that curcumin at concentrations described to be effective in the treatment of tumor cells and in inhibiting death of retinal neurons (,10 mM) has adverse effects on retinal pigment epithelial (RPE) cells
Treatment of the cultures with curcumin for 6 h resulted in a significant (P,0.05) decrease in the gene expression of vascular endothelial growth factor (VEGF) compared to control
Summary
The natural phenolic compound curcumin (diferuloylmethane), the yellow pigment of turmeric and an ingredient in curry powders, has a long history of use in traditional Asian medicine for a wide variety of disorders. Curcumin influences multiple intracellular signaling pathways and has both antioxidant and prooxidant effects in dependence on the concentration of the compound [10,11,12,13]. It induces apoptosis of cancer cells by activation of procaspases and the release of cytochrome c from mitochondria [14,15,16]. Both antioxidant and prooxidant activities were shown to be involved in the anticancer activity of curcumin [10,11,12,13]. It has been found that curcumin may cause toxicity to non-transformed cells under some circumstances [9,17,18]
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