METHODOLOGY/PRINCIPAL FINDINGS: Cellular 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.
CONCLUSION: 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 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.