title: Zinc-pheophorbide a-highly efficient low-cost photosensitizer against human adenocarcinoma in cellular and animal models.
abstract: BACKGROUND
  Our previous study has shown a prolonged retention and accumulation of Zn-pheophorbide a, a water-soluble derivative of chlorophyll a, in tumor tissue (Szczygiel et al. [19]). This prompted us to further evaluate the phototherapeutic potential of this photosensitizer of excellent physicochemical properties.
  
  
  METHODS
  Cellular uptake of Zn-pheophorbide, its localization in cells, cytotoxicity, phototoxicity and cell death mechanisms were studied in human adenocarcinoma cell lines: A549, MCF-7 and LoVo. The PDT efficacy was tested against A549 tumors growing in nude mice.
  
  
  RESULTS
  Zn-pheophorbide a even at very low concentrations (∼1×10(-6)M) and at low light doses (5J/cm(2)) causes a strong photodynamic effect, leading to 100% cell mortality. Confocal microscopy showed that in contrast to most derivatives of chlorophyll, Zn-pheophorbide a does not localize to mitochondria. The photodynamic effects and the cell death mechanisms of Zn-pheophorbide a, its Mg analog (chlorophyllide a) and Photofrin were compared on the A549 cells. Zn-pheophorbide a showed the strongest photodynamic effect, at low dose killing all A549 cells via apoptosis and necrosis. The very high anti-cancer potential of Zn-pheophorbide was confirmed in a photodynamic treatment of the A549 tumors. They either regressed or were markedly inhibited for up to 4 months after the treatment, resulting, on average, in a 5-fold decrease in tumor volume.
  
  
  CONCLUSIONS
  These results show that Zn-pheophorbide a is a very promising low-cost, synthetically easily accessible, second generation photosensitizer against human cancer.
authors.affiliation: Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University, Gronostajowa 7, Krakow 30-307, Poland.
authors.forename: Monika
authors.initials: M
authors.lastname: Jakubowska
authors.forename: Małgorzata
authors.initials: M
authors.lastname: Szczygieł
authors.forename: Dominika
authors.initials: D
authors.lastname: Michalczyk-Wetula
authors.forename: Anna
authors.initials: A
authors.lastname: Susz
authors.forename: Grażyna
authors.initials: G
authors.lastname: Stochel
authors.forename: Martyna
authors.initials: M
authors.lastname: Elas
authors.forename: Leszek
authors.initials: L
authors.lastname: Fiedor
authors.forename: Krystyna
authors.initials: K
authors.lastname: Urbanska
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy* / Q000191:economics / Q000473:pathology*; D000818:Animals; D045744:Cell Line, Tumor; D002734:Chlorophyll / Q000031:analogs & derivatives* / Q000191:economics / Q000627:therapeutic use; D004195:Disease Models, Animal; D006801:Humans; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D010778:Photochemotherapy / Q000191:economics / Q000379:methods*; D017319:Photosensitizing Agents / Q000191:economics / Q000627:therapeutic use*; D016896:Treatment Outcome; D015032:Zinc / Q000191:economics / Q000627:therapeutic use*
chemical_list: D017319:Photosensitizing Agents; D002734:Chlorophyll; C032623:pheophorbide a; D015032:Zinc
keywords: Human adenocarcinoma; Photodynamic therapy; Zn-pheophorbide