Identification of polyphenols that repair the ultraviolet-B-induced DNA damage via SIRT1-dependent XPC/XPA activation

Abstract

Ultraviolet (UV)-B is an established etiological cause of skin damage. SIRT1, a mammalian SIR2 homolog localized in the nucleus and cytosol, plays a protective role in UVB-induced DNA damage. In this study, we established a method of screening foods and food ingredients, which augment the SIRT1 promoter in HaCaT cells, where we used recombinant HaCaT cells transduced with the vector expressing EGFP under the control of SIRT1 promoter. We identified four SIRT1-augmenting pomegranate-derived polyphenols (ellagic acid, punicalin, punicalagin, and urolithin A). All of these contributed to the proliferation of UVB-irradiated HaCaT cells. Punicalagin and urolithin A removed UVB-induced cyclobutane pyrimidine dimers (CPD) by activating nucleotide excision repair (NER). Both punicalagin and urolithin A upregulated NER-related XPC expression and XPA deacetylation level in a SIRT1-dependent manner. In the present study, we attempted to elucidate the mechanisms underlying the repair of UVB-damaged HaCaT cells by pomegranate-derived polyphenols.

Keywords

• Pomegranate
• Punicalagin
• Urolithin A
• SIRT1
• DNA damage
• XPA/XPC