title: Mechanism and efficiency of cell death of type II photosensitizers: effect of zinc chelation.
abstract: A series of meso-substituted tetra-cationic porphyrins, which have methyl and octyl substituents, was studied in order to understand the effect of zinc chelation and photosensitizer subcellular localization in the mechanism of cell death. Zinc chelation does not change the photophysical properties of the photosensitizers (all molecules studied are type II photosensitizers) but affects considerably the interaction of the porphyrins with membranes, reducing mitochondrial accumulation. The total amount of intracellular reactive species induced by treating cells with photosensitizer and light is similar for zinc-chelated and free-base porphyrins that have the same alkyl substituent. Zinc-chelated porphyrins, which are poorly accumulated in mitochondria, show higher efficiency of cell death with features of apoptosis (higher MTT response compared with trypan blue staining, specific acridine orange/ethidium bromide staining, loss of mitochondrial transmembrane potential, stronger cytochrome c release and larger sub-G1 cell population), whereas nonchelated porphyrins, which are considerably more concentrated in mitochondria, triggered mainly necrotic cell death. We hypothesized that zinc-chelation protects the photoinduced properties of the porphyrins in the mitochondrial environment.
authors.affiliation: Departamento de Bioquímica, Instituto de Química-Universidade de São Paulo, São Paulo, Brasil.
authors.forename: Christiane
authors.initials: C
authors.lastname: Pavani
authors.forename: Yassuko
authors.initials: Y
authors.lastname: Iamamoto
authors.forename: Maurício S
authors.initials: MS
authors.lastname: Baptista
mesh_terms: D000165:Acridine Orange; D001692:Biological Transport / Q000187:drug effects / Q000528:radiation effects; D016923:Cell Death / Q000187:drug effects / Q000528:radiation effects; D002462:Cell Membrane / Q000187:drug effects / Q000528:radiation effects; D002470:Cell Survival / Q000187:drug effects / Q000528:radiation effects; D002614:Chelating Agents / Q000737:chemistry / Q000494:pharmacology*; D045304:Cytochromes c / Q000032:analysis; D004996:Ethidium; D005562:Formazans; D016193:G1 Phase / Q000187:drug effects / Q000528:radiation effects; D006367:HeLa Cells; D006801:Humans; D008027:Light; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects* / Q000528:radiation effects; D008928:Mitochondria / Q000187:drug effects* / Q000378:metabolism / Q000528:radiation effects; D055668:Photochemical Processes; D017319:Photosensitizing Agents / Q000737:chemistry / Q000494:pharmacology*; D011166:Porphyrins / Q000737:chemistry / Q000494:pharmacology*; D017382:Reactive Oxygen Species / Q000378:metabolism; D013778:Tetrazolium Salts; D015032:Zinc / Q000737:chemistry*
chemical_list: D002614:Chelating Agents; D005562:Formazans; D017319:Photosensitizing Agents; D011166:Porphyrins; D017382:Reactive Oxygen Species; D013778:Tetrazolium Salts; C079782:MTT formazan; D045304:Cytochromes c; D004996:Ethidium; D000165:Acridine Orange; D015032:Zinc