Sublethal UVB Induces DNA Lesions and Pro-Apoptotic Gene Transcription in Human Keratinocytes: Attenuation by a Mixture of Plant Extracts

Abstract

Ultraviolet B (UVB) radiation is a potent environmental factor in skin pathogenesis as it modulates oxidative burst, gene expression and proliferation/apoptosis of human normal keratinocytes. In the absence of cell apoptosis, sublethal UVB is shown to induce significant increase of mitochondrial and nuclear DNA lesions as quantified by increased apurinic/apyrimidinic sites together with transcriptomic modulation of pro-apoptosis/survival genes. These effects may be attenuated by cell pretreatment with extracts from three various plants: Papaver rhoeas, Passiflora incarnata and Anchusa arvensis or their mixture. Extracts variably decreased UVB-induced mitochondrial and nuclear DNA lesions in normal human keratincoytes. When mixed together, higher reduction of DNA lesions has been observed at lower extracts’ concentrations, compared to each extract alone which suggested their synergy. Furthermore, sublethal UVB-induced transcriptomic modulation was significantly prevented by cell preincubation with extract mixture through coordinated reduction of pro-apoptotic gene transcription while increasing pro-survival related transcripts. Finally, extract mixture protected keratinocytes against lethal UVB dose. This work reveals sublethal UVB-mediated lesions at both DNA and RNA levels in human keratinocytes and the ability of appropriate plant-derived sunscreen to reduce cell injury.