title: Zinc coproporphyrin I derived from meconium has an antitumor effect associated with singlet oxygen generation.
abstract: BACKGROUND
  Zinc coproporphyrin I (ZnCP-I) is a photosensitive molecule and a major component of meconium. Here, we examined the effects of ZnCP-I as a potential photosensitizer in photodynamic therapy for tumors.
  
  
  METHODS
  (1) Aqueous ZnCP-I was irradiated with a pulsed YAG-SHG laser (wavelength: 532 nm)/YAG-SHG dye laser (wavelength: 566 nm). (2) HeLa cells were incubated in 200 mM ZnCP-I, and accumulation of ZnCP-I in HeLa cells was evaluated with ZnCP-I-specific fluorescence over 500 nm. (3) Aqueous ZnCP-I was administered intravenously to HeLa tumor-bearing mice at a dose of 10.2 mg/kg body weight. The tumors were irradiated with a filtered halogen lamp (wavelength: 580 nm) at 100 J/cm(2) 20 min after administration.
  
  
  RESULTS
  (1) An intense near-infrared emission spectrum was observed at around 1,270 nm after irradiation. The emission intensity was proportional to the laser power between 10 and 80 mW and was completely inhibited by addition of NaN3, a singlet oxygen scavenger. (2) ZnCP-I-specific fluorescence was detected in the HeLa cell cytoplasm. (3) Irradiated tumors treated with ZnCP-I were mostly necrotized.
  
  
  CONCLUSIONS
  ZnCP-I accumulated in tumor cells, produced singlet oxygen upon irradiation, and necrotized the tumor cells. These results suggest that ZnCP-I may be an effective photosensitizer.
authors.affiliation: Department of Gynecology, Hamamatsu Rosai Hospital, Hamamatsu, Japan. epss@f7.dion.ne.jp
authors.forename: Hidechika
authors.initials: H
authors.lastname: Ozawa
authors.forename: Toshihiko
authors.initials: T
authors.lastname: Asahina
authors.forename: Hirotake
authors.initials: H
authors.lastname: Murakami
authors.forename: Chidzuko
authors.initials: C
authors.lastname: Yaguchi
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Kohmura
authors.forename: Eiji
authors.initials: E
authors.lastname: Kohno
authors.forename: Toru
authors.initials: T
authors.lastname: Hirano
authors.forename: Kentaro
authors.initials: K
authors.lastname: Horiuchi
authors.forename: Naoaki
authors.initials: N
authors.lastname: Tamura
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Sugihara
authors.forename: Hidekazu
authors.initials: H
authors.lastname: Ooi
authors.forename: Naohiro
authors.initials: N
authors.lastname: Kanayama
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000037:antagonists & inhibitors / Q000494:pharmacology / Q000528:radiation effects / Q000627:therapeutic use*; D001692:Biological Transport; D003306:Coproporphyrins / Q000037:antagonists & inhibitors / Q000494:pharmacology / Q000528:radiation effects / Q000627:therapeutic use*; D005260:Female; D016166:Free Radical Scavengers / Q000494:pharmacology; D006367:HeLa Cells; D006801:Humans; D054025:Lasers, Dye / Q000627:therapeutic use; D053844:Lasers, Solid-State / Q000627:therapeutic use; D008470:Meconium / Q000737:chemistry*; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009336:Necrosis; D009369:Neoplasms / Q000188:drug therapy* / Q000473:pathology; D016877:Oxidants / Q000037:antagonists & inhibitors / Q000494:pharmacology / Q000528:radiation effects / Q000627:therapeutic use; D010778:Photochemotherapy; D017319:Photosensitizing Agents / Q000037:antagonists & inhibitors / Q000494:pharmacology / Q000528:radiation effects / Q000627:therapeutic use*; D026082:Singlet Oxygen / Q000737:chemistry*; D023041:Xenograft Model Antitumor Assays; D015032:Zinc / Q000737:chemistry / Q000494:pharmacology / Q000528:radiation effects / Q000627:therapeutic use
chemical_list: D000970:Antineoplastic Agents; D003306:Coproporphyrins; D016166:Free Radical Scavengers; D016877:Oxidants; D017319:Photosensitizing Agents; D026082:Singlet Oxygen; C031467:coproporphyrin I; D015032:Zinc