title: Regulated necrosis in HeLa cells induced by ZnPc photodynamic treatment: a new nuclear morphology.
abstract: Photodynamic therapy (PDT) is a cancer treatment modality based on the administration of a photosensitizer (PS), which accumulates preferentially in tumor cells. Subsequent irradiation of the neoplastic area triggers a cascade of photochemical reactions that leads to the formation of highly reactive oxygen species responsible for cell inactivation. Photodynamic treatments in vitro are performed with the PS, zinc-phthalocyanine (ZnPc). The PS is near the plasma membrane during uptake and internalization. Inactivation clearly occurs by a necrotic process, manifested by nuclear pyknosis, negative TUNEL and Annexin V assays and non-relocation of cytochrome c. In contrast, by increasing the incubation time, ZnPc is accumulated in the Golgi apparatus and produces cell inactivation with characteristics of apoptosis and necrosis: TUNEL positive, relocated cytochrome c and negative Annexin V assay. This type of death produces a still undescribed granulated nuclear morphology, which is different from that of necrosis or apoptosis. This morphology is inhibited by necrostatin-1, a specific inhibitor of regulated necrosis.
authors.affiliation: Department of Biology, University Autonomous of Madrid, 28049 Madrid, Spain. jorge.soriano@uam.es.
authors.forename: Jorge
authors.initials: J
authors.lastname: Soriano
authors.affiliation: Department of Biology, University Autonomous of Madrid, 28049 Madrid, Spain. angeles.villanueva@uam.es.
authors.forename: Angeles
authors.initials: A
authors.lastname: Villanueva
authors.affiliation: Department of Biology, University Autonomous of Madrid, 28049 Madrid, Spain. juancarlos.stockert@uam.es.
authors.forename: Juan Carlos
authors.initials: JC
authors.lastname: Stockert
authors.affiliation: Department of Biology, University Autonomous of Madrid, 28049 Madrid, Spain. magdalena.canete@uam.es.
authors.forename: Magdalena
authors.initials: M
authors.lastname: Cañete
mesh_terms: D001692:Biological Transport; D016923:Cell Death / Q000187:drug effects / Q000528:radiation effects; D002467:Cell Nucleus / Q000187:drug effects / Q000473:pathology / Q000528:radiation effects; D002470:Cell Survival / Q000187:drug effects / Q000528:radiation effects; D004305:Dose-Response Relationship, Drug; D006367:HeLa Cells; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology; D007211:Indoles / Q000378:metabolism / Q000494:pharmacology*; D054833:Isoindoles; D009336:Necrosis / Q000209:etiology* / Q000473:pathology*; D009942:Organometallic Compounds / Q000378:metabolism / Q000494:pharmacology*; D010778:Photochemotherapy; D017319:Photosensitizing Agents / Q000378:metabolism / Q000494:pharmacology*; D017967:Zinc Compounds
chemical_list: D007093:Imidazoles; D007211:Indoles; D054833:Isoindoles; D009942:Organometallic Compounds; D017319:Photosensitizing Agents; D017967:Zinc Compounds; C507699:necrostatin-1; C052159:Zn(II)-phthalocyanine