Inhibitory Effect of Epigallocatechin Gallate (EGCG), Resveratrol, and Curcumin on Proliferation of Human Retinal Pigment Epithelial Cells In Vitro

Abstract

Purpose: To investigate potential inhibitory effects of three polyphenolic agents, epigallocatechin gallate (EGCG; from green tea), resveratrol (from red wine), and curcumin (from turmeric), on the proliferation of human retinal pigment epithelial (RPE) cells and to elucidate unwanted effects.

Methods: ARPE19 cells and primary human RPE cells were cultured in the presence of various concentrations of EGCG, resveratrol, or curcumin, and compared with controls. The number of viable cells was determined after 24, 48, and 72 hr by flow cytometrical enumeration. Furthermore, cell division was measured by dye dilution assay using carboxyfluorescein succinimidyl ester (CFSE), cell death by Hoechst 33258 staining, and apoptosis by staining for active caspase 3/7 and 8.

Results: The three drugs inhibited the increase of RPE cell numbers at all time points, with resveratrol being the most efficient and curcumin being the least efficient. EGCG inhibited cell proliferation with intermediate efficiency, and showed little induction of cell death. Resveratrol almost completely suppressed cell proliferation, and induced RPE cell necrosis and caspase 3/7- and caspase 8-dependent apoptosis. Curcumin inhibited RPE cell increase exclusively by inducing caspase 3/7-dependent but caspase 8-independent cell death and necrosis.

Conclusions: All three polyphenols tested reduced the absolute number of cells, but had different effects on cell proliferation, apoptosis, and necrosis. Resveratrol was most potent and EGCG induced the least cell death. These polyphenols may aid treatment of proliferative vitreoretinopathy (PVR).

KEYWORDS::

• Apoptosis
• Carboxyfluorescein succinimidyl ester
• Curcumin
• Epigallocatechin gallate
• Proliferation
• Resveratrol
• Retinal pigment epithelial cells

ACKNOWLEDGMENTS

The authors thank Parand Widmar and Claudine Strack for excellent technical assistance and Dr. Daniel R. Engel for advice on cell culture systems. Primary human retinal pigment epithelial cells (pRPE) were kindly provided by Dr. Boris Stanzel. We acknowledge support by the IMMEI flow-cytometry core facility. This work was supported by “Aktion Kampf der Erblindung” (AKdE). A.P.T. was supported by DFG grant Ku1063/5.

Declaration of interest: The authors report no conflict of interest. The authors alone are responsible for the content and writing of the paper.