[PMID]: | 28559202 |
[Au] Autor: | Chen YY; Tsai CF; Tsai MC; Hsu YW; Lu FJ |
[Ad] Endereço: | Institute of Medicine, College of Medicine, Chung Shan Medical University, Taichung City, Taiwan. |
[Ti] Título: | Inhibitory effects of rosmarinic acid on pterygium epithelial cells through redox imbalance and induction of extrinsic and intrinsic apoptosis. |
[So] Source: | Exp Eye Res;160:96-105, 2017 Jul. |
[Is] ISSN: | 1096-0007 |
[Cp] País de publicação: | England |
[La] Idioma: | eng |
[Ab] Resumo: | Pterygium is a common tumor-like ocular disease, which may be related to exposure to chronic ultraviolet (UV) radiation. Although the standard treatment for pterygium is surgical intervention, the recurrence rate of pterygium is high when no effective inhibitory drug is used after surgery. Rosmarinic acid (RA) is a polyphenol antioxidant with many biological activities, including anti-UV and anti-tumor properties. This study aimed to examine the inhibitory effects of RA on pterygium epithelial cells (PECs). Methylthiazolyldiphenyl-tetrazolium bromide (MTT) assay was used to examine the cell cytotoxicity of PECs after RA treatment. A fluorescent probe, DCFH-DA (2',7'-dichlorofluorescin diacetate), was stained with PECs to measure intracellular reactive oxygen species (ROS) levels. Antioxidant activity assays were used to measure the levels of superoxide dismutase (SOD) and catalase (CAT) in PECs. Western blot analysis was used to determine the protein expression of nuclear factor E2-related factor 2 (Nrf2), heme oxygenase 1 (HO-1), quinone acceptor oxidoreductase 1 (NQO1), and apoptosis-associated proteins. RA significantly reduced the cell viability of the PECs. Treatment with RA remarkably increased the Nrf2 protein expression levels in the nucleus, HO-1 and NQO1 protein expression levels, and the activities of SOD and CAT. As a result, intracellular ROS levels in PECs were decreased. Additionally, the induction of extrinsic apoptosis on PECs by RA was associated with increasing expressions levels of Fas, Fas-associated protein with death domain (FADD), tumor necrosis factor-alpha (TNF-α), and caspase 8 protein. Moreover, the induction of intrinsic apoptotic cell death in PECs was confirmed through upregulation of cytochrome c, Bax, caspase 9, and caspase 3 and downregulation of Bcl-2 and pro-caspase 3. Our study demonstrated that RA could inhibit the viability of PECs through regulation of extrinsic and intrinsic apoptosis pathways. Therefore, RA may have potential as a therapeutic medication for pterygium. |
[Mh] Termos MeSH primário: |
Apoptose/efeitos dos fármacos Cinamatos/farmacologia Depsídeos/farmacologia Células Epiteliais/efeitos dos fármacos Pterígio/tratamento farmacológico
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[Mh] Termos MeSH secundário: |
Antioxidantes/farmacologia Western Blotting Sobrevivência Celular Células Cultivadas Convertases de Complemento C3-C5 Células Epiteliais/metabolismo Células Epiteliais/patologia Seres Humanos Oxirredução Pterígio/metabolismo Pterígio/patologia Espécies Reativas de Oxigênio/metabolismo Transdução de Sinais Superóxido Dismutase/metabolismo
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[Pt] Tipo de publicação: | JOURNAL ARTICLE |
[Nm] Nome de substância:
| 0 (Antioxidants); 0 (Cinnamates); 0 (Depsides); 0 (Reactive Oxygen Species); EC 1.15.1.1 (Superoxide Dismutase); EC 3.4.21.- (Complement C3-C5 Convertases); MQE6XG29YI (rosmarinic acid) |
[Em] Mês de entrada: | 1708 |
[Cu] Atualização por classe: | 170809 |
[Lr] Data última revisão:
| 170809 |
[Sb] Subgrupo de revista: | IM |
[Da] Data de entrada para processamento: | 170601 |
[St] Status: | MEDLINE |
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