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Protective Effect of Combined Caffeic Acid Phenethyl Ester and Bevacizumab Against Hydrogen Peroxide-Induced Oxidative Stress in Human RPE Cells.
Curr Eye Res. 2017 12; 42(12):1659-1666.CE

Abstract

PURPOSE

This study aimed to evaluate the protective effects of caffeic acid phenethyl ester (CAPE) and combined CAPE-bevacizumab against oxidative stress induced by hydrogen peroxide (H2O2) in human retinal pigment epithelium.

METHODS

ARPE-19 cells were pretreated with 5, 10, and 30 μM CAPE alone and in combination with bevacizumab for 3 h, then exposed to H2O2 for 16 h. Cell viability was evaluated with the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Vascular endothelial growth factor (VEGF) protein levels in the medium were measured using a human VEGF ELISA kit. Total antioxidant status (TAS) and total oxidant status (TOS) were measured in ARPE-19 cells using the test kit from Rel Assay. Expression levels of VEGF, Bax, Bcl-2, cytochrome c, apoptotic protease activating factor-1 (apaf-1), and caspase-3 were determined using reverse transcription polymerase chain reaction.

RESULTS

Pretreatment of ARPE-19 cells with 30 μM CAPE and combined CAPE-bevacizumab reduced H2O2 mediated cell death. H2O2-induced oxidative stress increased TOS and VEGF production, which was significantly inhibited by CAPE and the CAPE-bevacizumab combination. VEGF, Bax, cytochrome c, apaf-1, and caspase-3 gene expressions were significantly decreased in cells pretreated with 5, 10, and 30 μM CAPE and combined CAPE-bevacizumab compared to the H2O2 group. In addition, Bcl-2 expression was significantly increased in both the CAPE and CAPE-bevacizumab combination groups compared to the H2O2 group.

CONCLUSIONS

CAPE has a protective effect on ARPE-19 cells against oxidative stress, and VEGF protein level and expression can be decreased by incubation with different concentrations of CAPE. These results demonstrate that CAPE suppresses the mitochondria-mediated apoptosis in ARPE-19 cells under oxidative stress. In addition, the use of CAPE in combination with bevacizumab has an additive effect.

Authors+Show Affiliations

a Department of Ophthalmology , Faculty of Medicine , Mersin University , Mersin , Turkey.b Department of Biochemistry , Faculty of Pharmacy , Trakya University , Edirne , Turkey.c Department of Pharmacology , Faculty of Medicine, Kahramanmaraş Sütçü İmam University , K. Maraş , Turkey.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

28937872

Citation

Dinc, Erdem, et al. "Protective Effect of Combined Caffeic Acid Phenethyl Ester and Bevacizumab Against Hydrogen Peroxide-Induced Oxidative Stress in Human RPE Cells." Current Eye Research, vol. 42, no. 12, 2017, pp. 1659-1666.
Dinc E, Ayaz L, Kurt AH. Protective Effect of Combined Caffeic Acid Phenethyl Ester and Bevacizumab Against Hydrogen Peroxide-Induced Oxidative Stress in Human RPE Cells. Curr Eye Res. 2017;42(12):1659-1666.
Dinc, E., Ayaz, L., & Kurt, A. H. (2017). Protective Effect of Combined Caffeic Acid Phenethyl Ester and Bevacizumab Against Hydrogen Peroxide-Induced Oxidative Stress in Human RPE Cells. Current Eye Research, 42(12), 1659-1666. https://doi.org/10.1080/02713683.2017.1368085
Dinc E, Ayaz L, Kurt AH. Protective Effect of Combined Caffeic Acid Phenethyl Ester and Bevacizumab Against Hydrogen Peroxide-Induced Oxidative Stress in Human RPE Cells. Curr Eye Res. 2017;42(12):1659-1666. PubMed PMID: 28937872.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Protective Effect of Combined Caffeic Acid Phenethyl Ester and Bevacizumab Against Hydrogen Peroxide-Induced Oxidative Stress in Human RPE Cells. AU - Dinc,Erdem, AU - Ayaz,Lokman, AU - Kurt,Akif Hakan, Y1 - 2017/09/22/ PY - 2017/9/25/pubmed PY - 2018/1/27/medline PY - 2017/9/23/entrez KW - Age related macular degeneration KW - CAPE KW - bevacizumab KW - caffeic acid phenethyl ester KW - oxidative stress KW - retinal pigment epithelium SP - 1659 EP - 1666 JF - Current eye research JO - Curr Eye Res VL - 42 IS - 12 N2 - PURPOSE: This study aimed to evaluate the protective effects of caffeic acid phenethyl ester (CAPE) and combined CAPE-bevacizumab against oxidative stress induced by hydrogen peroxide (H2O2) in human retinal pigment epithelium. METHODS: ARPE-19 cells were pretreated with 5, 10, and 30 μM CAPE alone and in combination with bevacizumab for 3 h, then exposed to H2O2 for 16 h. Cell viability was evaluated with the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Vascular endothelial growth factor (VEGF) protein levels in the medium were measured using a human VEGF ELISA kit. Total antioxidant status (TAS) and total oxidant status (TOS) were measured in ARPE-19 cells using the test kit from Rel Assay. Expression levels of VEGF, Bax, Bcl-2, cytochrome c, apoptotic protease activating factor-1 (apaf-1), and caspase-3 were determined using reverse transcription polymerase chain reaction. RESULTS: Pretreatment of ARPE-19 cells with 30 μM CAPE and combined CAPE-bevacizumab reduced H2O2 mediated cell death. H2O2-induced oxidative stress increased TOS and VEGF production, which was significantly inhibited by CAPE and the CAPE-bevacizumab combination. VEGF, Bax, cytochrome c, apaf-1, and caspase-3 gene expressions were significantly decreased in cells pretreated with 5, 10, and 30 μM CAPE and combined CAPE-bevacizumab compared to the H2O2 group. In addition, Bcl-2 expression was significantly increased in both the CAPE and CAPE-bevacizumab combination groups compared to the H2O2 group. CONCLUSIONS: CAPE has a protective effect on ARPE-19 cells against oxidative stress, and VEGF protein level and expression can be decreased by incubation with different concentrations of CAPE. These results demonstrate that CAPE suppresses the mitochondria-mediated apoptosis in ARPE-19 cells under oxidative stress. In addition, the use of CAPE in combination with bevacizumab has an additive effect. SN - 1460-2202 UR - https://www.unboundmedicine.com/medline/citation/28937872/Protective_Effect_of_Combined_Caffeic_Acid_Phenethyl_Ester_and_Bevacizumab_Against_Hydrogen_Peroxide_Induced_Oxidative_Stress_in_Human_RPE_Cells_ L2 - https://www.tandfonline.com/doi/full/10.1080/02713683.2017.1368085 DB - PRIME DP - Unbound Medicine ER -