Cytotoxic Effects of Curcumin in Human Retinal Pigment Epithelial Cells

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.

Modulation of the Proteasome Pathway by Nano-Curcumin and Curcumin in Retinal Pigment Epithelial Cells

“…Our study demonstrates significant cytotoxic effects of standard curcumin in RPE cells at concentrations >20 μM. These findings are in agreement with the data of previous studies in which curcumin exhibited pro-apoptotic effects in RPE cells at concentrations of approximately 20 μM [10,11]. These concentrations are in the same concentration range that is supposed to be effective in cancer cells [48][49][50][51][52].…”

“…However, recent reports of curcumin-mediated retinal cytotoxicity [10][11][12][13] could imply that chronic intake of curcumin negatively affects retinal function. The aims of this study are the following: (1) to assess and characterize the cytotoxic and oxidative effects of nano-curcumin and standard curcumin in RPE cells in vitro, and (2) to investigate the in vitro effects of nano-curcumin and standard curcumin on proteasome expression and activity in RPE cells, to ascertain whether they can be used as proteasome-modulating agents in retinal disorders.…”

Turmeric (Curcuma longa) and its major constituent (curcumin) as nontoxic and safe substances: Review

“…In a study for investigation of cytotoxic effects of curcumin on normal cells (spleen lymphocytes and NIH3T3) and cancer cells (EL4 and MCF7), curcumin at concentrations of 5 to 80 nmol/ml demonstrated that the uptake of curcumin in cancer cells was higher than normal cells so cytotoxic effects of curcumin on cancer cells is more than normal cells (Kunwar et al, ). Research projects on human epithelial pigment cells revealed that concentrations higher than 10 μM of curcumin reduced proliferation of cells, and also, 1 to 50 μM of curcumin decreased the number of living and viable cells (Hollborn et al, ). On vascular smooth muscle cells (VSMCs) and endothelial cells that isolated from aorta, curcumin showed toxic effects on normal cells and inhibited cell proliferation at the concentration of 5 μM.…”

The generation of induced pluripotent stem cells for macular degeneration as a drug screening platform: identification of curcumin as a protective agent for retinal pigment epithelial cells against oxidative stress

“…After administration of curcumin, the expression of these antioxidant genes was significantly up-regulated (Figure 6A). Recent evidences have demonstrated that curcumin may modulate growth factor expression and can act as a therapeutic agent (Epstein et al, 2010; Hollborn et al, 2013). PDGF, VEGF, and IGFBP-2 have been shown to be involved in regular RPE functions or retinal diseases (Epstein et al, 2010; Hollborn et al, 2013).…”