title: Cytotoxic effects of curcumin in human retinal pigment epithelial cells.
abstract: BACKGROUND
  Curcumin 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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Ophthalmology and Eye Hospital, University of Leipzig, Leipzig, Germany. hollbm@medizin.uni-leipzig.de
authors.forename: Margrit
authors.initials: M
authors.lastname: Hollborn
authors.forename: Rui
authors.initials: R
authors.lastname: Chen
authors.forename: Peter
authors.initials: P
authors.lastname: Wiedemann
authors.forename: Andreas
authors.initials: A
authors.lastname: Reichenbach
authors.forename: Andreas
authors.initials: A
authors.lastname: Bringmann
authors.forename: Leon
authors.initials: L
authors.lastname: Kohen
mesh_terms: D051017:Apoptosis Regulatory Proteins / Q000235:genetics; D016923:Cell Death / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002633:Chemotaxis / Q000187:drug effects; D003474:Curcumin / Q000633:toxicity*; D016207:Cytokines / Q000378:metabolism; D003603:Cytotoxins / Q000633:toxicity*; D053938:DNA Fragmentation / Q000187:drug effects; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D042541:Intracellular Space / Q000187:drug effects / Q000378:metabolism; D055213:Retinal Pigment Epithelium / Q000166:cytology*; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D051017:Apoptosis Regulatory Proteins; D016207:Cytokines; D003603:Cytotoxins; D003474:Curcumin
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