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Proceedings Article

Ursolic acid mediates photosensitization by initiating mitochondrial-dependent apoptosis

[+] Author Affiliations
Yuan-Hao Lee, Exing Wang, Neeru Kumar, Randolph D. Glickman

Univ. of Texas Health Science Ctr. at San Antonio (United States)

Proc. SPIE 8579, Optical Interactions with Tissue and Cells XXIV, 85790F (February 15, 2013); doi:10.1117/12.2000225
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From Conference Volume 8579

  • Optical Interactions with Tissue and Cells XXIV
  • E. Duco Jansen; Robert J. Thomas
  • San Francisco, California, USA | February 02, 2013

abstract

The signaling pathways PI3K/Akt and MAPK play key roles in transcription, translation and carcinogenesis, and may be activated by light exposure. These pathways may be modulated or inhibited by naturally-occurring compounds, such as the triterpenoid, ursolic acid (UA). Previously, the transcription factors p53 and NF-kB, which transactivate mitochondrial apoptosis-related genes, were shown to be differentially modulated by UA. Our current work indicates that UA causes these effects via the mTOR and insulin-mediated pathways. UA-modulated apoptosis, following exposure to UV radiation, is observed to correspond to differential levels of oxidative stress in retinal pigment epithelial (RPE) and skin melanoma (SM) cells. Flow cytometry analysis, DHE (dihydroethidium) staining and membrane permeability assay showed that UA pretreatment potentiated cell cycle arrest and radiation-induced apoptosis selectively on SM cells while DNA photo-oxidative damage (i.e. strand breakage) was reduced, presumably by some antioxidant activity of UA in RPE cells. The UA-mediated NF-κB activation in SM cells was reduced by rapamycin pretreatment, which indicates that these agents exert inter-antagonistic effects in the PI3K/Akt/mTOR pathway. In contrast, the antagonistic effect of UA on the PI3K/Akt pathway was reversed by insulin leading to greater NF-κB and p53 activation in RPE cells. MitoTracker, a mitochondrial functional assay, indicated that mitochondria in RPE cells experienced reduced oxidative stress while those in SM cells exhibited increased oxidative stress upon UA pretreatment. When rapamycin administration was followed by UA, mitochondrial oxidative stress was increased in RPE cells but decreased in SM cells. These results indicate that UA modulates p53 and NF-κB, initiating a mitogenic response to radiation that triggers mitochondria-dependent apoptosis. © (2013) COPYRIGHT Society of Photo-Optical Instrumentation Engineers (SPIE). Downloading of the abstract is permitted for personal use only.
Citation

Yuan-Hao Lee ; Exing Wang ; Neeru Kumar and Randolph D. Glickman
" Ursolic acid mediates photosensitization by initiating mitochondrial-dependent apoptosis ", Proc. SPIE 8579, Optical Interactions with Tissue and Cells XXIV, 85790F (February 15, 2013); doi:10.1117/12.2000225; http://dx.doi.org/10.1117/12.2000225


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