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Certain phytonutrients are known to confer protection and immunosuppression against radiation insults.
Radiation-induced reactive oxygen species (ROS) can either lead to the destruction of normal tissue cells, or induce
tumor radioresistance by activating ROS scavenging proteins. To identify whether the triterpene phytonutrient,
ursolic acid, reduces radiation-induced damage in normal cells and promotes the apoptosis of malignant cells, we
investigated the biologic mechanisms and effect of radiation-cell interaction with or without treatment with ursolic
acid in human skin melanoma cells (ATCC CRL-11147TM) and transformed human retinal pigment epithelial
(hTERT-RPE) cells. UV-VIS light was employed to investigate the efficacy of ursolic acid in altering cellular
viability by modulations of p53 and NF-κB p65 signaling. Cell response was investigated by changes in proliferative
activity and free radical generation assessed by
2',7'-dichlorofluorescin liquid chromatography. Ursolic acid
pretreatment strongly increased the level of p53 and decreased the level of phosphorylated p65 leading to enhanced
cell death of skin melanoma cells in response to UV-VIS exposure. In contrast, ursolic acid appeared to downregulate
p53 levels without disturbing NF-κB activation along with an increase of oxidative stress in hTERT-RPE
cells. These findings indicate that ursolic acid may beneficially increase the radiosensitivity of tumor cells while
potentiating a photoprotective effect on benign cells through differential effects on the NF-κB and p53 signaling
pathways.
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