Parthenolide protects human lens epithelial cells from oxidative stress-induced apoptosis via inhibition of activation of caspase-3 and caspase-9

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