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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...

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Autores principales: Huang, Wan-Rong, Zhang, Yue, Tang, Xin
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2014
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.
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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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