title: Protoporphyrin IX-dependent photodynamic production of endogenous ROS stimulates cell proliferation.
abstract: Photodynamic therapy using methyl 5-aminolevulinate (MAL) as a precursor of the photosensitizing agent protoporphyrin IX is widely used in clinical practice for the treatment of different pathologies, including cancer. In this therapeutic modality, MAL treatment promotes the forced accumulation of the endogenous photoactive compound protoporphyrin IX in target malignant cells. Subsequent irradiation of treated tissues with an appropriate visible light source induces the production of reactive oxygen species (ROS) that, once accumulated above a critical level, promote cell death. Here we demonstrate that a photodynamic treatment with low MAL concentrations can be used to promote a moderate production of endogenous ROS, which efficiently stimulates cell growth in human immortalized keratinocytes (HaCaT). We also show that this proliferative response requires Src kinase activity and is associated to a transient induction of cyclin D1 expression. Taken together, these results demonstrate for the first time that a combination of light and a photoactive compound can be used to modulate cell cycle progression through Src kinase activation and that a moderate intracellular increase of photogenerated ROS efficiently stimulates cell proliferation.
authors.affiliation: Departamento de Biología, Facultad de Ciencias, Universidad Autónoma de Madrid, Madrid, Spain.
authors.forename: Alfonso
authors.initials: A
authors.lastname: Blázquez-Castro
authors.forename: Elisa
authors.initials: E
authors.lastname: Carrasco
authors.forename: María I
authors.initials: MI
authors.lastname: Calvo
authors.forename: Pedro
authors.initials: P
authors.lastname: Jaén
authors.forename: Juan Carlos
authors.initials: JC
authors.lastname: Stockert
authors.forename: Angeles
authors.initials: A
authors.lastname: Juarranz
authors.forename: Francisco
authors.initials: F
authors.lastname: Sánz-Rodríguez
authors.forename: Jesús
authors.initials: J
authors.lastname: Espada
mesh_terms: D000622:Aminolevulinic Acid / Q000008:administration & dosage / Q000031:analogs & derivatives; D002453:Cell Cycle; D049109:Cell Proliferation / Q000528:radiation effects; D006801:Humans; D015603:Keratinocytes / Q000166:cytology; D000074624:NADPH Oxidase 1; D019255:NADPH Oxidases / Q000037:antagonists & inhibitors / Q000378:metabolism; D010778:Photochemotherapy; D017319:Photosensitizing Agents / Q000528:radiation effects; D011524:Protoporphyrins / Q000096:biosynthesis* / Q000528:radiation effects; D017382:Reactive Oxygen Species / Q000037:antagonists & inhibitors / Q000528:radiation effects; D014407:Tumor Cells, Cultured; D019061:src-Family Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism
chemical_list: D017319:Photosensitizing Agents; D011524:Protoporphyrins; D017382:Reactive Oxygen Species; C475457:methyl 5-aminolevulinate; D000622:Aminolevulinic Acid; C028025:protoporphyrin IX; D000074624:NADPH Oxidase 1; D019255:NADPH Oxidases; C402799:NOX1 protein, human; D019061:src-Family Kinases