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  • Shikonin inhibits the proliferation of human lens epithelial cells by inducing apoptosis through ROS and caspase-dependent pathway.

Shikonin inhibits the proliferation of human lens epithelial cells by inducing apoptosis through ROS and caspase-dependent pathway.

Molecules (Basel, Switzerland) (2014-06-26)
Wan-Rong Huang, Yue Zhang, Xin Tang
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.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
N-Acetyl-L-cysteine, Sigma Grade, ≥99% (TLC), powder
Sigma-Aldrich
N-Acetyl-L-cysteine, BioXtra, ≥99% (TLC)
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N-Acetyl-L-cysteine, BioReagent, suitable for cell culture
Sigma-Aldrich
JC-1, solid
Supelco
N-Acetyl-L-cysteine, Pharmaceutical Secondary Standard; Certified Reference Material
Acetylcysteine, European Pharmacopoeia (EP) Reference Standard
USP
Acetylcysteine, United States Pharmacopeia (USP) Reference Standard