Caffeic acid phenethyl ester reduces the secretion of vascular endothelial growth factor through the inhibition of the ROS, PI3K and HIF-1α signaling pathways in human retinal pigment epithelial cells under hypoxic conditions

Paeng,Sung  Hwa; Jung,Won-Kyo; Park,Won  Sun; Lee,Dae-Sung; Kim,Gi-Young; Choi,Yung  Hyun; Seo,Su-Kil; Jang,Won  Hee; Choi,Jung  Sik; Lee,Young-Min; Park,Saegwang; Choi,Il-Whan

doi:10.3892/ijmm.2015.2116

Caffeic acid phenethyl ester reduces the secretion of vascular endothelial growth factor through the inhibition of the ROS, PI3K and HIF-1α signaling pathways in human retinal pigment epithelial cells under hypoxic conditions

Authors:
- Sung Hwa Paeng
- Won-Kyo Jung
- Won Sun Park
- Dae-Sung Lee
- Gi-Young Kim
- Yung Hyun Choi
- Su-Kil Seo
- Won Hee Jang
- Jung Sik Choi
- Young-Min Lee
- Saegwang Park
- Il-Whan Choi
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Affiliations: Department of Neurosurgery, Busan Paik Hospital, Inje University College of Medicine, Busan, Republic of Korea, Department of Biomedical Engineering, and Center for Marine-Integrated Biomedical Technology (BK21 Plus), Pukyong National University, Busan, Republic of Korea, Department of Physiology, Kangwon National University School of Medicine, Chuncheon, Gangwon, Republic of Korea, Marine Biodiversity Institute of Korea, Seocheon, Chungcheongnam-do, Republic of Korea, Laboratory of Immunobiology, Department of Marine Life Sciences, Jeju National University, Jeju, Republic of Korea, Department of Biochemistry, College of Oriental Medicine, Dongeui University, Busan, Republic of Korea, Department of Microbiology, Busan Paik Hospital, Inje University College of Medicine, Busan, Republic of Korea, Department of Biochemistry, Busan Paik Hospital, Inje University College of Medicine, Busan, Republic of Korea, Department of Internal Medicine, Busan Paik Hospital, Inje University College of Medicine, Busan, Republic of Korea
Published online on: February 27, 2015 https://doi.org/10.3892/ijmm.2015.2116
Pages: 1419-1426

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Abstract

Choroidal neovascularization (CNV) can lead to progressive and severe visual loss. Vascular endothelial growth factor (VEGF) promotes the development of CNV. Caffeic acid phenethyl ester (CAPE), a biologically active component of the honeybee (Apis mellifera) propolis, has been demonstrated to have several interesting biological regulatory properties. The objective of this study was to determine whether treatment with CAPE results in the inhibition of the production of vascular endothelial growth factor (VEGF) in retinal pigment epithelial cells (RPE cells) under hypoxic conditions and to explore the possible underlying mechanisms. An in vitro experimental model of hypoxia was used to mimic an ischemic microenvironment for the RPE cells. Human RPE cells (ARPE-19) were exposed to hypoxia with or without CAPE pre-treatment. ARPE-19 cells were used to investigate the pathway involved in the regulation of VEGF production under hypoxic conditions, based on western blot analysis, enzyme-linked immunosorbent assay (ELISA) and electrophoretic mobility shift assay (EMSA). The amount of VEGF released from the hypoxia‑exposed cells was significantly higher than that of the normoxic controls. Pre-treatment with CAPE suppressed the hypoxia-induced production of VEGF in the ARPE-19 cells, and this effect was inhibited through the attenuation of reactive oxygen species (ROS) production, and the inhibition of phosphoinositide 3-kinase (PI3K)/AKT and hypoxia-inducible factor-1α (HIF-1α) expression. These in vitro findings suggest that CAPE may prove to be a novel anti-angiogenic agent for the treatment of diseases associated with CNV.

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