title: Pro-oxidant and Antioxidant Effects in Photodynamic Therapy: Cells Recognise that Not All Exogenous ROS Are Alike.
abstract: Photodynamic therapy (PDT) uses light, photosensitizer molecules and oxygen to generate reactive oxygen species (ROS) that kill cancer cells. Redaporfin, a new photosensitizer in clinical trials, generates both singlet oxygen and superoxide ions. We report the potentiation of redaporfin-PDT in combination with ascorbate and with the inhibition of antioxidant enzymes in A549 (human lung adenocarcinoma) and CT26 (mouse colon adenocarcinoma) cells. The addition of ascorbate and the inhibition of superoxide dismutase (SOD) strongly increased the phototoxicity of redaporfin towards A549 cells but not towards CT26 cells. The inhibition of catalase and the depletion of the glutathione pool also potentiate redaporfin-PDT towards A549 cells. The lower SOD activity of A549 cells might explain this difference. SOD activity levels may be explored to increase the selectivity and efficacy of PDT with photosensitizers that generate radical species.
authors.affiliation: Chemistry Department, Universidade de Coimbra, Rua Larga, 3004-535, Coimbra, Portugal.
authors.forename: Helder T
authors.identifier: 0000-0002-8006-7189
authors.initials: HT
authors.lastname: Soares
authors.affiliation: Chemistry Department, Universidade de Coimbra, Rua Larga, 3004-535, Coimbra, Portugal.
authors.forename: Joana R S
authors.identifier: 0000-0001-9245-949X
authors.initials: JR
authors.lastname: Campos
authors.affiliation: Chemistry Department, Universidade de Coimbra, Rua Larga, 3004-535, Coimbra, Portugal.
authors.forename: Lígia C
authors.identifier: 0000-0003-0624-8819
authors.initials: LC
authors.lastname: Gomes-da-Silva
authors.affiliation: Luzitin SA, Ed. Bluepharma, 3045-016, Coimbra, Portugal.
authors.forename: Fábio A
authors.initials: FA
authors.lastname: Schaberle
authors.affiliation: Faculty of Chemistry, Jagiellonian University, Ingardena 3, 30-060, Kraków, Poland.
authors.forename: Janusz M
authors.identifier: 0000-0002-8791-7035
authors.initials: JM
authors.lastname: Dabrowski
authors.affiliation: Chemistry Department, Universidade de Coimbra, Rua Larga, 3004-535, Coimbra, Portugal. lgarnaut@ci.uc.pt.
authors.forename: Luis G
authors.identifier: 0000-0002-3223-4819
authors.initials: LG
authors.lastname: Arnaut
mesh_terms: D000072283:A549 Cells; D000230:Adenocarcinoma / Q000188:drug therapy; D000077192:Adenocarcinoma of Lung; D000818:Animals; D000975:Antioxidants / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology; D001205:Ascorbic Acid / Q000494:pharmacology; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology; D008027:Light; D008175:Lung Neoplasms / Q000188:drug therapy; D051379:Mice; D018384:Oxidative Stress / Q000187:drug effects*; D010778:Photochemotherapy; D017319:Photosensitizing Agents / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D011166:Porphyrins / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use; D017382:Reactive Oxygen Species / Q000378:metabolism*; D013449:Sulfonamides / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use; D013482:Superoxide Dismutase / Q000037:antagonists & inhibitors / Q000378:metabolism
chemical_list: D000975:Antioxidants; D017319:Photosensitizing Agents; D011166:Porphyrins; D017382:Reactive Oxygen Species; D013449:Sulfonamides; D006861:Hydrogen Peroxide; D013482:Superoxide Dismutase; D001205:Ascorbic Acid; C000610760:redaporfin
keywords: catalase; hydroxyl radical; photodynamic therapy; radical ions; singlet oxygen; superoxide ion