title: Photodynamic Therapy Mediated by a Novel Chlorin Derivative, TONS 501-Na, in EMT6 cells.
abstract: The lipophilic photosensitizer, TONS 501, is a novel porphyrin-derived methyl ester that was developed for photodynamic antimicrobial chemotherapy. This study developed a hydrophilic and anionic porphyrin salt of this compound (TONS 501-Na) for use in photodynamic therapy (PDT). This chlorin derivative is synthesized from the protoporphyrin IX dimethyl ester.
  
  
  
  We investigated the in vitro cytotoxic effects of TONS 501-Na-mediated PDT on EMT6 mouse breast cancer cells. EMT6 cells were incubated with 0-100 μg/ml TONS 501-Na for 24 h prior to replacing the culture medium and exposing the cells to 6 mW/cm2diode laser irradiation at 0-13 J/cm2to induce PDT. Morphological changes and cell viability were evaluated 24 h after PDT. The percentages of apoptotic cells were evaluated 4 h and 24 h after PDT.
  
  
  
  The concentrations of TONS 501-Na that killed 50% of EMT6 cells after exposure to light doses of 0, 0.4, 3, 6, or 13 J/cm2were 84.6, 33.2, 18, 8.2, and 2.2 μg/ml, respectively. Tumor cells exposed to PDT showed chromatin condensation and fragmentation. The percentages of apoptotic cells increased in a TONS 501-Na concentration-dependent manner in the PDT group, and were significantly higher than those in the control group or in cells treated with TONS 501-Na or laser irradiation alone.
  
  
  
  TONS 501-Na-mediated PDT induced mouse breast cancer cell death in a concentration-dependent manner. Future studies should evaluate the in vivo pharmacokinetics, tissue distribution, and photodynamic effects of TONS 501-Na.
authors.affiliation: Department of Veterinary Clinical Medicine, School of Veterinary Medicine, Tottori University, Tottori, Japan tosaki@muses.tottori-u.ac.jp.
authors.forename: Tomohiro
authors.initials: T
authors.lastname: Osaki
authors.affiliation: Porphyrin Laboratory, Okayama, Japan.
authors.forename: Isao
authors.initials: I
authors.lastname: Sakata
authors.affiliation: Faculty of Bioscience and Bioindustry, Tokushima University, Tokushima, Japan.
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Uto
authors.affiliation: Department of Veterinary Clinical Medicine, School of Veterinary Medicine, Tottori University, Tottori, Japan.
authors.forename: Kazuo
authors.initials: K
authors.lastname: Azuma
authors.affiliation: Department of Veterinary Clinical Medicine, School of Veterinary Medicine, Tottori University, Tottori, Japan.
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Murahata
authors.affiliation: Department of Veterinary Clinical Medicine, School of Veterinary Medicine, Tottori University, Tottori, Japan.
authors.forename: Takeshi
authors.initials: T
authors.lastname: Tsuka
authors.affiliation: Department of Veterinary Clinical Medicine, School of Veterinary Medicine, Tottori University, Tottori, Japan.
authors.forename: Norihiko
authors.initials: N
authors.lastname: Itoh
authors.affiliation: Department of Veterinary Clinical Medicine, School of Veterinary Medicine, Tottori University, Tottori, Japan.
authors.forename: Tomohiro
authors.initials: T
authors.lastname: Imagawa
authors.affiliation: Department of Veterinary Clinical Medicine, School of Veterinary Medicine, Tottori University, Tottori, Japan.
authors.forename: Yoshiharu
authors.initials: Y
authors.lastname: Okamoto
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects* / Q000528:radiation effects; D005260:Female; D008027:Light; D015674:Mammary Neoplasms, Animal / Q000188:drug therapy* / Q000473:pathology / Q000532:radiotherapy; D051379:Mice; D010778:Photochemotherapy; D017319:Photosensitizing Agents / Q000494:pharmacology*; D011166:Porphyrins / Q000737:chemistry* / Q000494:pharmacology*; D014407:Tumor Cells, Cultured
chemical_list: C576983:13,17-bis(1-carboxypropionyl)carbamoylethyl-3-ethenyl-2-hydroxy-3-hydroxyiminoethlidene-2,7,12,18-tetramethylporphyrin; D017319:Photosensitizing Agents; D011166:Porphyrins; C006969:chlorin
keywords: Apoptosis; TONS 501-Na; photodynamic therapy