Caffeic acid prevents UVB radiation induced photocarcinogenesis through regulation of PTEN signaling in human dermal fibroblasts and mouse skin

Previously, we proved that caffeic acid (CA), a major dietary phenolic acid, prevents skin carcinogenesis by modulating inflammatory signaling in mouse skin. However, the actual mechanisms of CA against UVB (280–320 nm) induced photocarcinogenesis remains unclear. The present results confirms that C...

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Published in:Toxicology and applied pharmacology 2018-08, Vol.352, p.87-96
Main Authors: Balupillai, Agilan, Nagarajan, Rajendra Prasad, Ramasamy, Karthikeyan, Govindasamy, Kanimozhi, Muthusamy, Ganesan
Format: Article
Language:English
Subjects:
Caffeic acid
Nucleotide excision repair
Photocarcinogenesis
UV radiation
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Summary:Previously, we proved that caffeic acid (CA), a major dietary phenolic acid, prevents skin carcinogenesis by modulating inflammatory signaling in mouse skin. However, the actual mechanisms of CA against UVB (280–320 nm) induced photocarcinogenesis remains unclear. The present results confirms that CA significantly inhibits single UVB-induced CPDs formation, oxidative DNA damage, ROS generation and frequency of apoptotic cell death in human dermal fibroblasts (HDFa). Furthermore, CA prevents UVB-induced expression of PI3K and AKT kinases through activation of PTEN which subsequently promotes XPC dependant NER proteins such as XPC, XPE, TFIIH (p44) and ERCC1 in HDFa cells and mouse skin tissue. Further, CA directly activates PTEN through hydrogen bond and hydrophobic interactions. Taken together, these findings suggest that CA prevents UVB-induced photodamage through the activation of PTEN expression in human dermal fibroblasts and mouse skin. •CA prevents UVB induced DNA damage and apoptotic signaling in HDFa cells.•CA restores UVB induced NER genes thereby inhibit CPDs.•CA treatment suppressed UVB induced PI3K, AKT signaling.•CA prevents UVB induced photocarcinogenesis probably through activation of PTEN.
ISSN:0041-008X
1096-0333
DOI:10.1016/j.taap.2018.05.030