title: Arbutin, an intracellular hydroxyl radical scavenger, protects radiation-induced apoptosis in human lymphoma U937 cells.
abstract: Ionizing radiation (IR) can generate reactive oxygen species (ROS). Excessive ROS have the potential to damage cellular macromolecules including DNA, proteins, and lipids and eventually lead to cell death. In this study, we evaluated the potential of arbutin, a drug chosen from a series of traditional herbal medicine by measuring intracellular hydroxyl radical scavenging ability in X-irradiated U937 cells. Arbutin (hydroquinone-β-D-glucopyranoside), a naturally occurring glucoside of hydroquinone, has been traditionally used to treat pigmentary disorders. However, there are no reports describing the effect of arbutin on IR-induced apoptosis. We confirmed that arbutin can protect cells from apoptosis induced by X-irradiation. The combination of arbutin and X-irradiation could reduce intracellular hydroxyl radical production and prevent mitochondrial membrane potential loss. It also could down-regulate the expression of phospho-JNK, phospho-p38 in whole cell lysate and activate Bax in mitochondria. Arbutin also inhibits cytochrome C release from mitochondria to cytosol. To verify the role of JNK in X-irradiation-induced apoptosis, the cells were pretreated with a JNK inhibitor, and found that JNK inhibitor could reduce apoptosis induced by X-irradiation. Taken together, our data indicate that arbutin plays an anti-apoptotic role via decreasing intracellular hydroxyl radical production, inhibition of Bax-mitochondria pathway and activation of the JNK/p38 MAPK pathway.
authors.affiliation: Department of Pathology, The 2nd Affiliated Hospital of Harbin Medical University, Nangang District, Harbin, 150081, China.
authors.forename: Li-Hua
authors.initials: LH
authors.lastname: Wu
authors.forename: Peng
authors.initials: P
authors.lastname: Li
authors.forename: Qing-Li
authors.initials: QL
authors.lastname: Zhao
authors.forename: Jin-Lan
authors.initials: JL
authors.lastname: Piao
authors.forename: Yu-Fei
authors.initials: YF
authors.lastname: Jiao
authors.forename: Makoto
authors.initials: M
authors.lastname: Kadowaki
authors.forename: Takashi
authors.initials: T
authors.lastname: Kondo
mesh_terms: D017209:Apoptosis / Q000187:drug effects* / Q000528:radiation effects; D001104:Arbutin / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D053181:Caspase 8 / Q000378:metabolism; D016166:Free Radical Scavengers / Q000494:pharmacology*; D006801:Humans; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D010766:Phosphorylation; D011837:Radiation-Protective Agents / Q000494:pharmacology*; D017382:Reactive Oxygen Species / Q000378:metabolism; D020298:U937 Cells; D019014:fas Receptor / Q000378:metabolism; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
chemical_list: C491901:FAS protein, human; D016166:Free Radical Scavengers; D011837:Radiation-Protective Agents; D017382:Reactive Oxygen Species; D019014:fas Receptor; D001104:Arbutin; D048031:JNK Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases; D053181:Caspase 8