title: Resveratrol couples apoptosis with autophagy in UVB-irradiated HaCaT cells.
abstract: 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.
authors.affiliation: Department of Molecular Medicine and Medical Biotechnologies, University of Naples "Federico II", Naples, Italy.
authors.forename: Nicoletta
authors.initials: N
authors.lastname: Vitale
authors.forename: Annamaria
authors.initials: A
authors.lastname: Kisslinger
authors.forename: Simona
authors.initials: S
authors.lastname: Paladino
authors.forename: Claudio
authors.initials: C
authors.lastname: Procaccini
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Matarese
authors.forename: Giovanna Maria
authors.initials: GM
authors.lastname: Pierantoni
authors.forename: Francesco Paolo
authors.initials: FP
authors.lastname: Mancini
authors.forename: Donatella
authors.initials: D
authors.lastname: Tramontano
mesh_terms: D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects* / Q000528:radiation effects; D051017:Apoptosis Regulatory Proteins / Q000235:genetics / Q000378:metabolism; D001343:Autophagy / Q000187:drug effects* / Q000528:radiation effects; D000071186:Beclin-1; D053181:Caspase 8 / Q000378:metabolism; D002461:Cell Line, Transformed; D049109:Cell Proliferation / Q000187:drug effects / Q000528:radiation effects; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D008869:Microtubule-Associated Proteins / Q000235:genetics / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects / Q000528:radiation effects; D010588:Phagosomes / Q000187:drug effects / Q000378:metabolism / Q000528:radiation effects; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism; D059748:Proteolysis; D017382:Reactive Oxygen Species / Q000378:metabolism; D000077185:Resveratrol; D015398:Signal Transduction / Q000187:drug effects; D013267:Stilbenes / Q000494:pharmacology*; D014466:Ultraviolet Rays
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D051017:Apoptosis Regulatory Proteins; C491997:BECN1 protein, human; D000071186:Beclin-1; C477012:MAP1LC3A protein, human; D008565:Membrane Proteins; D008869:Microtubule-Associated Proteins; D017382:Reactive Oxygen Species; D013267:Stilbenes; D006861:Hydrogen Peroxide; D011065:Poly(ADP-ribose) Polymerases; D053181:Caspase 8; D000077185:Resveratrol