title: Shikonin inhibits the proliferation of human lens epithelial cells by inducing apoptosis through ROS and caspase-dependent pathway.
abstract: 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.
authors: Tianjin Eye Hospital, Clinic College of Ophthalmology, Tianjin Medical University, Tianjin 300020, China. scarlethwang@aliyun.com.
authors: Wan-Rong
authors: WR
authors: Huang
authors: Tianjin Eye Hospital, Clinic College of Ophthalmology, Tianjin Medical University, Tianjin 300020, China. zmoon0225@126.com.
authors: Yue
authors: Y
authors: Zhang
authors: Tianjin Eye Hospital, Clinic College of Ophthalmology, Tianjin Medical University, Tianjin 300020, China. tangprofessorx@163.com.
authors: Xin
authors: X
authors: Tang
mesh_terms: D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects*; D053148:Caspase 3 / Q000378:metabolism; D053179:Caspase 7 / Q000378:metabolism; D053453:Caspase 9 / Q000378:metabolism; D061945:Caspase Inhibitors / Q000494:pharmacology*; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects*; D004365:Drugs, Chinese Herbal / Q000494:pharmacology; D004847:Epithelial Cells / Q000166:cytology; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D006801:Humans; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism; D007908:Lens, Crystalline / Q000166:cytology / Q000254:growth & development*; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D009285:Naphthoquinones / Q000494:pharmacology*; D010766:Phosphorylation / Q000187:drug effects; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000096:biosynthesis; D017382:Reactive Oxygen Species / Q000378:metabolism*; D051028:bcl-2-Associated X Protein / Q000096:biosynthesis; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D061945:Caspase Inhibitors; D004365:Drugs, Chinese Herbal; D009285:Naphthoquinones; D019253:Proto-Oncogene Proteins c-bcl-2; D017382:Reactive Oxygen Species; D051028:bcl-2-Associated X Protein; C016101:shikonin; D048049:Extracellular Signal-Regulated MAP Kinases; D048031:JNK Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases; D053148:Caspase 3; D053179:Caspase 7; D053453:Caspase 9