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

Agilan Balupillai; Rajendra Prasad Nagarajan; Karthikeyan Ramasamy; Kanimozhi Govindasamy; Ganesan Muthusamy

doi:10.1016/j.taap.2018.05.030

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

Toxicol Appl Pharmacol. 2018 Aug 1:352:87-96. doi: 10.1016/j.taap.2018.05.030. Epub 2018 May 23.

Authors

Agilan Balupillai¹, Rajendra Prasad Nagarajan², Karthikeyan Ramasamy¹, Kanimozhi Govindasamy¹, Ganesan Muthusamy¹

Affiliations

¹ Department of Biochemistry and Biotechnology, Annamalai University, Annamalainagar 608002, Tamil Nadu, India.
² Department of Biochemistry and Biotechnology, Annamalai University, Annamalainagar 608002, Tamil Nadu, India. Electronic address: drprasadnr@gmail.com.

PMID: 29802912
DOI: 10.1016/j.taap.2018.05.030

Abstract

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.

Keywords: Caffeic acid; Nucleotide excision repair; Photocarcinogenesis; UV radiation.

MeSH terms

Animals
Anticarcinogenic Agents / pharmacology*
Apoptosis / drug effects
Caffeic Acids / pharmacology*
Cell Transformation, Neoplastic / drug effects*
Cell Transformation, Neoplastic / metabolism
Cell Transformation, Neoplastic / pathology
Cell Transformation, Neoplastic / radiation effects
DNA Damage / drug effects
DNA Repair / drug effects
DNA Repair Enzymes / metabolism
Fibroblasts / drug effects*
Fibroblasts / enzymology
Fibroblasts / pathology
Fibroblasts / radiation effects
Humans
Mice
Neoplasms, Experimental / enzymology
Neoplasms, Experimental / pathology
Neoplasms, Experimental / prevention & control*
Neoplasms, Radiation-Induced / enzymology
Neoplasms, Radiation-Induced / pathology
Neoplasms, Radiation-Induced / prevention & control*
Oxidative Stress / drug effects
Oxidative Stress / radiation effects
PTEN Phosphohydrolase / metabolism*
Signal Transduction / drug effects*
Signal Transduction / radiation effects
Skin / drug effects*
Skin / enzymology
Skin / pathology
Skin / radiation effects
Skin Neoplasms / enzymology
Skin Neoplasms / pathology
Skin Neoplasms / prevention & control*
Ultraviolet Rays / adverse effects*

Substances

Anticarcinogenic Agents
Caffeic Acids
PTEN Phosphohydrolase
PTEN protein, human
DNA Repair Enzymes
caffeic acid