ORIGINAL ARTICLE

Cell Research (2007): 565-571
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Parthenolide protects human lens epithelial cells from oxidative stress-induced apoptosis via inhibition of activation of caspase-3 and caspase-9

Hangping Yao¹, Xiajing Tang², Xueting Shao¹, Lei Feng¹, Nanping Wu¹, Ke Yao²

Correspondence: Ke Yao Tel: +86-571-87783908; Fax: +86-571-87783908; E-mail: xlren@zju.edu.cn

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The apoptosis of lens epithelial cells has been proposed as the common basis of cataract formation, with oxidative stress as the major cause. This study was performed to investigate the protective effect of the herbal constituent parthenolide against oxidative stress-induced apoptosis of human lens epithelial (HLE) cells and the possible molecular mechanisms involved. HLE cells (SRA01-04) were incubated with 50 μM H₂O₂ in the absence or presence of different doses of parthenolide (10, 20 and 50 μM). To study apoptosis, the cells were assessed by morphologic examination and Annexin V-propidium iodide double staining flow cytometry; to investigate the underlying molecular mechanisms, the expression of caspase-3 and caspase-9 were assayed by Western blot and quantitative RT-PCR, and the activities of caspase-3 and caspase-9 were measured by a Chemicon caspase colorimetric activity assay kit. Stimulated with H₂O₂ for 18 h, a high fraction of HLE cells underwent apoptosis, while in the presence of parthenolide of different concentrations, dose-dependent blocking of HLE cell apoptosis was observed. The expression of caspase-3 and caspase-9 induced by H₂O₂ in HLE cells was significantly reduced by parthenolide both at the protein and mRNA levels, and the activation of caspase-3 and caspase-9 was also suppressed by parthenolide in a dose-dependent manner. In conclusion, parthenolide prevents HLE cells from oxidative stress-induced apoptosis through inhibition of the activation of caspase-3 and caspase-9, suggesting a potential protective effect against cataract formation.

Cell Research (2007) 17:565–571 doi: 10.1038/cr.2007.6; published online 6 March 2007

Keywords: parthenolide, human lens epithelial cells, apoptosis, caspase-3 and caspase-9