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Shikonin Inhibits the Proliferation of Human Lens Epithelial Cells by Inducing Apoptosis through ROS and Caspase-Dependent Pathway
Shikonin is a compound from the herbal plant Lithospermum erythrorhizon that has been proved to possess powerful anti-proliferative effect on many kinds of cancers and to be safe in in vivo study. Posterior capsular opacification (PCO), the most frequent complication of cataract surgery, is mainly c...
Autores principales: | , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2014
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6270879/ https://www.ncbi.nlm.nih.gov/pubmed/24962386 http://dx.doi.org/10.3390/molecules19067785 |
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author | Huang, Wan-Rong Zhang, Yue Tang, Xin |
author_facet | Huang, Wan-Rong Zhang, Yue Tang, Xin |
author_sort | Huang, Wan-Rong |
collection | PubMed |
description | Shikonin is a compound from the herbal plant Lithospermum erythrorhizon that has been proved to possess powerful anti-proliferative effect on many kinds of cancers and to be safe in in vivo study. Posterior capsular opacification (PCO), the most frequent complication of cataract surgery, is mainly caused by the uncontrolled proliferation of retained human lens epithelial cells (HLEs). In this study, we investigated the effect of shikonin on the proliferation of HLEs and explored its underlying mechanism of action. Shikonin significantly inhibited the proliferation of HLEs in a dose- and time-dependent manner. Its anti-proliferative effect was exerted through induction of apoptosis. Reactive oxygen species (ROS) generation played an essential role in this apoptotic process. Interestingly, scavenging of ROS completely blocked the apoptosis induced by shikonin. In addition, the treatment of shikonin in HLEs significantly increased the ratio of Bax/Bcl-2, disrupted mitochondria membrane potential (MMP) and activated caspases. The inhibition of caspase largely blocks the apoptosis. The changes of MAPK pathway were also demonstrated. Shikonin effectively inhibited the phosphorylation of ERK, while it activated the phosphorylation of JNK and p38. These results suggested that shikonin inhibited the proliferation of HLEs by inducing apoptosis through ROS generation and the caspase-dependent pathway and the MAPK pathway was also involved. |
format | Online Article Text |
id | pubmed-6270879 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2014 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-62708792018-12-21 Shikonin Inhibits the Proliferation of Human Lens Epithelial Cells by Inducing Apoptosis through ROS and Caspase-Dependent Pathway Huang, Wan-Rong Zhang, Yue Tang, Xin Molecules Article Shikonin is a compound from the herbal plant Lithospermum erythrorhizon that has been proved to possess powerful anti-proliferative effect on many kinds of cancers and to be safe in in vivo study. Posterior capsular opacification (PCO), the most frequent complication of cataract surgery, is mainly caused by the uncontrolled proliferation of retained human lens epithelial cells (HLEs). In this study, we investigated the effect of shikonin on the proliferation of HLEs and explored its underlying mechanism of action. Shikonin significantly inhibited the proliferation of HLEs in a dose- and time-dependent manner. Its anti-proliferative effect was exerted through induction of apoptosis. Reactive oxygen species (ROS) generation played an essential role in this apoptotic process. Interestingly, scavenging of ROS completely blocked the apoptosis induced by shikonin. In addition, the treatment of shikonin in HLEs significantly increased the ratio of Bax/Bcl-2, disrupted mitochondria membrane potential (MMP) and activated caspases. The inhibition of caspase largely blocks the apoptosis. The changes of MAPK pathway were also demonstrated. Shikonin effectively inhibited the phosphorylation of ERK, while it activated the phosphorylation of JNK and p38. These results suggested that shikonin inhibited the proliferation of HLEs by inducing apoptosis through ROS generation and the caspase-dependent pathway and the MAPK pathway was also involved. MDPI 2014-06-11 /pmc/articles/PMC6270879/ /pubmed/24962386 http://dx.doi.org/10.3390/molecules19067785 Text en © 2014 by the authors. licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution license (http://creativecommons.org/licenses/by/3.0/). |
spellingShingle | Article Huang, Wan-Rong Zhang, Yue Tang, Xin Shikonin Inhibits the Proliferation of Human Lens Epithelial Cells by Inducing Apoptosis through ROS and Caspase-Dependent Pathway |
title | Shikonin Inhibits the Proliferation of Human Lens Epithelial Cells by Inducing Apoptosis through ROS and Caspase-Dependent Pathway |
title_full | Shikonin Inhibits the Proliferation of Human Lens Epithelial Cells by Inducing Apoptosis through ROS and Caspase-Dependent Pathway |
title_fullStr | Shikonin Inhibits the Proliferation of Human Lens Epithelial Cells by Inducing Apoptosis through ROS and Caspase-Dependent Pathway |
title_full_unstemmed | Shikonin Inhibits the Proliferation of Human Lens Epithelial Cells by Inducing Apoptosis through ROS and Caspase-Dependent Pathway |
title_short | Shikonin Inhibits the Proliferation of Human Lens Epithelial Cells by Inducing Apoptosis through ROS and Caspase-Dependent Pathway |
title_sort | shikonin inhibits the proliferation of human lens epithelial cells by inducing apoptosis through ros and caspase-dependent pathway |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6270879/ https://www.ncbi.nlm.nih.gov/pubmed/24962386 http://dx.doi.org/10.3390/molecules19067785 |
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