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

Abstract

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 H 2 O 2 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 H 2 O 2 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 H 2 O 2 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.

Effect of estrogen replacement therapy on lens epithelial cell apoptosis in an experimental rat model

“…However, many studies have revealed a relationship between lens epithelial cell apoptosis and cataractogenesis [11][12][13][14][15]. In our study, we found increased lens epithelial cell apoptosis experimental menopause had been experimentially induced in our rat model.…”

“…Studies on the relationship between apoptosis and cataractogenesis in different animal models provide strong support for the hypothesis that stress-induced apoptosis is the common initiating event during cataractogenesis. An increase in lens epithelium cell apoptosis is thought to decrease the regulatory effect of the lens epithelium cells relative to that of the lens fibril cells, resulting in a decrease in the transparency of the lens [11][12][13][14][15]. It has been reported that estrogen protects pancreatic beta [16], retinal ganglion [17], neuronal [18], bone [19], and heart [20] cells via inhibition of apoptosis; however, no information is available in the literature on the effect of estrogen on lens epithelial cells.…”

Caspase-3 as an important factor in the early cytotoxic effect of nickel on oral mucosa cells in patients treated orthodontically

“…It has been shown that oxidative stress, which induces apoptosis, depends on the activation of caspase-3 in human lens epithelial cells, rat dopaminergic neuronal N27 cells and mice testicular cells [16][17][18]. Our immunohistochemical staining revealed a higher number of caspase-3 immunoreactive epithelial cells in clinically healthy participants one week after the attachment of orthodontic appliances.…”

Molecular basis of parthenolide-dependent proapoptotic activity in cancer cells.

“…Described above PN-mediated effects on JNK activity could be both pro-or antiapoptotic. It should be emphasized that PN action in normal cells augments cells viability and protects them from UVB- [52] or ROS-induced apoptosis [59,63,68]. In contrast, PN is toxic to abnormal cells.…”