The flavonoid, fisetin, inhibits UV radiation-induced oxidative stress and the activation of NF-кB and MAPK signaling in human lens epithelial cells

PURPOSE: Ultraviolet (UV) radiation-induced oxidative stress plays a significant role in the progression of cataracts. This study investigated the photoprotective effect of fisetin on UV radiation-induced oxidative stress in human lens epithelial cells and the possible molecular mechanism involved. METHODS: SRA01/04 cells exposed to different doses of ultraviolet B (UVB) were cultured with various concentrations of fisetin and subsequently monitored for cell viability by the 4,5-dimethylthiazol-2-yl-2,5-diphenyltetrazolium bromide (MTT) assay. The effect of fisetin on the generation of reactive oxygen species (ROS) of SRA01/04 cells was determined by flow cytometry. Translocation of nuclear factor kappa-B (NF-кB) was examined by immunocytochemistry. Expression of NF-кB/P65, inhibiter kappa B (IкB), and mitogen activated protein kinase (MAPK) proteins were measured by western blot. RESULTS: Treatment of SRA01/04 cells with fisetin inhibited UVB-induced cell death and the generation of ROS. Fisetin inhibited UVB-induced activation and translocation of NF-кB/p65, which was mediated through an inhibition of the degradation and activation of IкB. Fisetin also inhibited UVB-induced phosphorylation of the p38 and c-Jun N-terminal kinase (JNK) proteins of the MAPK family at various time points studied. CONCLUSIONS: The flavonoid, fisetin, could be useful in attenuation of UV radiation-induced oxidative stress and the activation of NF-кB and MAPK signaling in human lens epithelial cells, which suggests that fisetin has a potential protective effect against cataractogenesis.