Resveratrol Couples Apoptosis with Autophagy in UVB-Irradiated HaCaT Cells

• Published in: PloS one Vol. 8; no. 11; p. e80728
• Main Authors: Vitale, Nicoletta, Kisslinger, Annamaria, Paladino, Simona, Procaccini, Claudio, Matarese, Giuseppe, Pierantoni, Giovanna Maria, Mancini, Francesco Paolo, Tramontano, Donatella
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 19.11.2013; Public Library of Science (PLoS)
• Subjects: Antineoplastic Agents, Phytogenic - pharmacology; Antioxidants; Antioxidants (Nutrients); Apoptosis; Apoptosis - drug effects; Apoptosis - radiation effects; Apoptosis Regulatory Proteins - genetics; Apoptosis Regulatory Proteins - metabolism; Autophagy; Autophagy - drug effects; Autophagy - radiation effects; Beclin-1; Biotechnology; Cancer genetics; Caspase; Caspase 8 - metabolism; Caspase-8; Cell cycle; Cell death; Cell Line, Transformed; Cell proliferation; Cell Proliferation - drug effects; Cell Proliferation - radiation effects; Cellular signal transduction; Colorectal cancer; Deoxyribonucleic acid; DNA; DNA damage; Endocrinology; Gene expression; Humans; Hydrogen Peroxide - pharmacology; Inflammation; Inflammatory response; Irradiation; Keratinocytes; Kinases; Medicine; Melanoma; Membrane Proteins - genetics; Membrane Proteins - metabolism; Microtubule-Associated Proteins - genetics; Microtubule-Associated Proteins - metabolism; Oxidative stress; Oxidative Stress - drug effects; Oxidative Stress - radiation effects; Oxidizing agents; Oxygen; Phagocytosis; Phagosomes - drug effects; Phagosomes - metabolism; Phagosomes - radiation effects; Phosphorylation; Phytochemicals; Poly(ADP-ribose) Polymerases - metabolism; Proteins; Proteolysis; Radiation; Radiation (Physics); Radiation damage; Reactive oxygen species; Reactive Oxygen Species - metabolism; Resveratrol; Signal Transduction - drug effects; Skin; Skin cancer; Skin diseases; Stilbenes - pharmacology; Transduction; Transformation; Ultraviolet radiation; Ultraviolet Rays; Italy; Milan Italy
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0080728

UVB radiation causes about 90% of non-melanoma skin cancers by damaging DNA either directly or indirectly by increasing levels of reactive oxygen species (ROS). Skin, chronically exposed to both endogenous and environmental pro-oxidant agents, contains a well-organised system of chemical and enzymatic antioxidants. However, increased or prolonged free radical action can overwhelm ROS defence mechanisms, contributing to the development of cutaneous diseases. Thus, new strategies for skin protection comprise the use of food antioxidants to counteract oxidative stress. Resveratrol, a phytoalexin from grape, has gained a great interest for its ability to influence several biological mechanisms like redox balance, cell proliferation, signal transduction pathways, immune and inflammatory response. Therefore, the potential of resveratrol to modify skin cell response to UVB exposure could turn out to be a useful option to protect skin from sunlight-induced degenerative diseases. To investigate into this matter, HaCaT cells, a largely used model for human skin keratinocytes, were treated with 25 or 100 µM resveratrol for 2 and 24 hours prior to UVB irradiation (10 to 100 mJ/cm(2)). Cell viability and molecular markers of proliferation, oxidative stress, apoptosis, and autophagy were analyzed. In HaCaT cells resveratrol pretreatment: reduces UVB-induced ROS formation, enhances the detrimental effect of UVB on HaCaT cell vitality, increases UVB-induced caspase 8, PARP cleavage, and induces autophagy. These findings suggest that resveratrol could exert photochemopreventive effects by enhancing UVB-induced apoptosis and by inducing autophagy, thus reducing the odds that damaged cells could escape programmed cell death and initiate malignant transformation.