title: Hydrogen [corrected] peroxide-dependent photocytotoxicity by phloxine B, a xanthene-type food colorant.
abstract: BACKGROUND
  Phloxine B (PhB; 2',4',5',7'-tetrabromo-4,5,6,7-tetrachloro-fluorescein), an artificial xanthene colorant, has been used as a red coloring agent in drugs and cosmetics as well as foods in some countries. However, little effort has been devoted to the study of this colorant as a potentially useful medicinal agent.
  
  
  METHODS
  We investigated the daily light-induced photocytotoxicity of PhB in two human leukemia cells, HL-60 and Jurkat, and its underlying mechanisms by in vitro experiments using antioxidants. REUSLTS AND CONCLUSIONS: PhB inhibited cell proliferation more preferentially to HL-60 cells than to Jurkat cells. Co-treatment of catalase completely blocked the photocytotoxicity by PhB in HL-60 cells, whereas the effect of histidine was only partial, suggesting that hydrogen peroxide (H(2)O(2)), rather than singlet oxygen, might be a prerequisite for the PhB-induced HL-60 cell death. Actually, PhB produced a significant amount of H(2)O(2) in the media as well as in the cells in concentration- and light-dependent manners. Furthermore, methionine, a hypochlorous acid (HOCl) scavenger, also significantly attenuated the cytotoxicity in HL-60 cells, but not in Jurkat cells, indicating the involvement of myeloperoxidase (MPO)-dependent hypohalous acid formation during the photocytotoxicity. In vitro experiments revealed that halogenated tyrosine was generated from the reaction of bovine serum albumin with PhB and HL-60 cell lysate. The present findings suggested that PhB induced a differential photodynamic action in the MPO-containing leukemia cells through an H(2)O(2)-dependent mechanism.
  
  
  CONCLUSIONS
  Our findings provide new insights into the molecular mechanisms underlying the PhB-induced apoptosis and also evaluated PhB as a promising PDT agent.
authors.affiliation: Department of Biofunctional Chemistry, Division of Bioscience, Graduate School of Natural Science and Technology, Okayama University, Okayama 700-8530, Japan.
authors.forename: Hang
authors.initials: H
authors.lastname: Qi
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Takano
authors.forename: Yoji
authors.initials: Y
authors.lastname: Kato
authors.forename: Qian
authors.initials: Q
authors.lastname: Wu
authors.forename: Chiharu
authors.initials: C
authors.lastname: Ogata
authors.forename: Beiwei
authors.initials: B
authors.lastname: Zhu
authors.forename: Yoshiyuki
authors.initials: Y
authors.lastname: Murata
authors.forename: Yoshimasa
authors.initials: Y
authors.lastname: Nakamura
mesh_terms: D017209:Apoptosis / Q000187:drug effects; D015153:Blotting, Western; D053148:Caspase 3 / Q000378:metabolism; D002470:Cell Survival / Q000187:drug effects* / Q000528:radiation effects; D053938:DNA Fragmentation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D010697:Eosine I Bluish / Q000737:chemistry / Q000494:pharmacology*; D005456:Fluorescent Dyes / Q000737:chemistry / Q000494:pharmacology; D005505:Food Coloring Agents / Q000737:chemistry / Q000494:pharmacology*; D018922:HL-60 Cells; D006801:Humans; D006861:Hydrogen Peroxide / Q000378:metabolism* / Q000494:pharmacology; D006997:Hypochlorous Acid / Q000378:metabolism / Q000494:pharmacology; D019169:Jurkat Cells; D008027:Light; D015394:Molecular Structure; D000091402:Prohibitins; D014966:Xanthenes / Q000737:chemistry
chemical_list: D005456:Fluorescent Dyes; D005505:Food Coloring Agents; C000717328:PHB protein, human; D000091402:Prohibitins; D014966:Xanthenes; D006997:Hypochlorous Acid; D006861:Hydrogen Peroxide; D053148:Caspase 3; D010697:Eosine I Bluish