Hydogen peroxide-dependent photocytotoxicity by phloxine B,a xanthene-type food colorant |
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Authors: | Hang Qi Hiroshi Takano Yoji Kato Qian Wu Chiharu Ogata Beiwei Zhu Yoshiyuki Murata Yoshimasa Nakamura |
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Institution: | 1. Department of Biofunctional Chemistry, Division of Bioscience, Graduate School of Natural Science and Technology, Okayama University, Okayama 700–8530, Japan;2. Graduate School of Human Science and Environment, University of Hyogo, Himeji 670–0092, Japan;3. College of Food Technology, Dalian Polytechnic University, Dalian 116034, China |
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Abstract: | BackgroundPhloxine 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.MethodsWe 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 conclusionsPhB 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 (H2O2), rather than singlet oxygen, might be a prerequisite for the PhB-induced HL-60 cell death. Actually, PhB produced a significant amount of H2O2 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 H2O2-dependent mechanism.General significanceOur findings provide new insights into the molecular mechanisms underlying the PhB-induced apoptosis and also evaluated PhB as a promising PDT agent. |
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Keywords: | FDA Food and Drug Administration PhB phloxine B H2O2 hydrogen peroxide MPO myeloperoxidase H2DCF-DA 2&prime 7&prime -dichlorodihydrofluorescein diacetate FOX ferrous ion oxidation&ndash xylenol orange JNK cJun-N-terminal kinase HOCl hypochlorous acid HOX hypohalous acid diBr-Y dibromated tyrosine PDT Photodynamic therapy MAPK mitogen activated protein kinase ASK1 apoptosis signal regulating kinase 1 |
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