title: Two combined photosensitizers: a goal for more effective photodynamic therapy of cancer.
abstract: Photodynamic therapy (PDT) is a clinically approved therapeutic modality for the treatment of diseases characterized by uncontrolled cell proliferation, mainly cancer. It involves the selective uptake of a photosensitizer (PS) by neoplastic tissue, which is able to produce reactive oxygen species upon irradiation with light, leading to tumor regression. Here a synergistic cell photoinactivation is reported based on the simultaneous administration of two PSs, zinc(II)-phthalocyanine (ZnPc) and the cationic porphyrin meso-tetrakis(4-N-methylpyridyl)porphine (TMPyP) in three cell lines (HeLa, HaCaT and MCF-7), using very low doses of PDT. We detected changes from predominant apoptosis (without cell detachment) to predominant necrosis, depending on the light dose used (2.4 and 3.6 J/cm(2), respectively). Analysis of changes in cytoskeleton components (microtubules and F-actin), FAK protein, as well as time-lapse video microscopy evidenced that HeLa cells were induced to undergo apoptosis, without losing adhesion to the substrate. Moreover, 24 h after intravenous injection into tumor-bearing mice, ZnPc and TMPyP were preferentially accumulated in the tumor area. PDT with combined treatment produced significant retardation of tumor growth. We believe that this combined and highly efficient strategy (two PSs) may provide synergistic curative rates regarding conventional photodynamic treatments (with one PS alone).
authors.affiliation: Department of Biology, Faculty of Sciences, Autonomous University of Madrid, Madrid 28049, Spain.
authors.forename: P
authors.identifier: 0000000348156090
authors.initials: P
authors.lastname: Acedo
authors.affiliation: Department of Biology, Faculty of Sciences, Autonomous University of Madrid, Madrid 28049, Spain.
authors.forename: J C
authors.initials: JC
authors.lastname: Stockert
authors.affiliation: Department of Biology, Faculty of Sciences, Autonomous University of Madrid, Madrid 28049, Spain.
authors.forename: M
authors.initials: M
authors.lastname: Cañete
authors.affiliation: Department of Biology, Faculty of Sciences, Autonomous University of Madrid, Madrid 28049, Spain.
authors.forename: A
authors.initials: A
authors.lastname: Villanueva
mesh_terms: D000199:Actins / Q000378:metabolism; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D004307:Dose-Response Relationship, Radiation; D004357:Drug Synergism; D005260:Female; D051417:Focal Adhesion Kinase 1 / Q000378:metabolism; D006367:HeLa Cells; D006801:Humans; D007211:Indoles / Q000008:administration & dosage / Q000378:metabolism / Q000494:pharmacology*; D007275:Injections, Intravenous; D054833:Isoindoles; D061986:MCF-7 Cells; D051379:Mice; D008810:Mice, Inbred C57BL; D018715:Microscopy, Video; D008870:Microtubules / Q000187:drug effects / Q000378:metabolism; D009336:Necrosis; D009369:Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D009942:Organometallic Compounds / Q000008:administration & dosage / Q000378:metabolism / Q000494:pharmacology*; D010778:Photochemotherapy; D017319:Photosensitizing Agents / Q000008:administration & dosage / Q000378:metabolism / Q000494:pharmacology*; D011166:Porphyrins / Q000008:administration & dosage / Q000378:metabolism / Q000494:pharmacology*; D013997:Time Factors; D059008:Time-Lapse Imaging; D047368:Tumor Burden / Q000187:drug effects; D023041:Xenograft Model Antitumor Assays; D017967:Zinc Compounds
chemical_list: D000199:Actins; D007211:Indoles; D054833:Isoindoles; D009942:Organometallic Compounds; D017319:Photosensitizing Agents; D011166:Porphyrins; D017967:Zinc Compounds; C540459:meso-tetrakis(N-methylpyridinium-4-yl)porphyrin; C052159:Zn(II)-phthalocyanine; D051417:Focal Adhesion Kinase 1; C496050:PTK2 protein, human