Modulation of photochemical damage in normal and malignant cells by naturally occurring compounds

Certain phytochemicals, such as the stilbene, resveratrol (RES, found in red grapes and berries), and the triterpenoid, ursolic acid (UA, found in waxy berries and herbs such as rosemary and oregano), have antioxidant, anti-inflammatory and antiproliferative effects. Two human-derived cell lines, hTERT-RPE with a nonmalignant phenotype derived from retinal pigment epithelium, and ATCC CRL-11147 derived from a malignant skin melanoma, were used as in vitro models of photooxidative stress produced by exposure to the broadband output of a 150 W Hg vapor arc lamp at an irradiance of 19-26 mW cm ^-2. In untreated cells, UV-VIS broadband light exposure produced a loss of proliferative ability, an activation of NF-κB and an increase in protein carbonyl adducts at 24 h postexposure. Pretreatment of the cells with RES or UA at 1-2 μmsignificantly reduced the amount of phosphorylated NF-κB at 24 h postexposure. RES pretreatment reduced the burden of light-induced protein carbonyl adducts by up to 25% in exposed cells. UA treatment markedly increased the sensitivity of melanoma cells to UV radiation, while conferring some photoprotection to RPE cells. These observations indicate that phytochemicals modulate the cellular response to photochemical stress by interacting with specific cell-signaling pathways. There is heightened interest in naturally occurring compounds as potential therapeutic agents. One such compound is ursolic acid (UA), a triterpenoid found in common foods such as cranberries, apples, as well as rosemary and other herbs. When skin melanoma (SM) cells are treated with UA, they become more susceptible to UV and visible light exposure, in contrast to normal phenotype retinal pigment epithelial (RPE) cells, whose sensitivity to light damage is unchanged by UA treatment. The figure shows the appearance of SM and RPE cells 24 h following light exposure with or without UA pretreatment.