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Arbutin, an intracellular hydroxyl radical scavenger, protects radiation-induced apoptosis in human lymphoma U937 cells

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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.

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Abbreviations

IR:

Ionizing radiation

ROS:

Reactive oxygen species

HPF:

Hydroxyphenyl fluorescein

DAF-2 DA:

Diaminofluorescein-2 diacetate

HE:

Hydroethidine

MMP:

Mitochondrial membrane potential

TMRM:

Tetramethylrhodamine methyl ester

PI:

Propidium iodide

FITC:

Fluorescein isothiocyanate

pNA:

p-nitroanilide

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Acknowledgments

This research was supported by a Grant-in-Aid for the Cooperative Research Project from Joint Usage/Research Center (Joint Usage/Research Center for Science-Based Natural Medicine) Institute of Natural Medicine. University of Toyama; and in part by the International Exchange Fund of The Sugitani Campus (Medical and Pharmacy) (A) 2012, University of Toyama, Japan.

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Authors and Affiliations

  1. Department of Pathology, The 2nd Affiliated Hospital of Harbin Medical University, Nangang District, Harbin, 150081, China

    Li-Hua Wu & Yu-Fei Jiao

  2. Department of Radiological Sciences, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, Sugitani 2630, Toyama, 930-0194, Japan

    Peng Li, Qing-Li Zhao, Jin-Lan Piao & Takashi Kondo

  3. Department of Gastrointestinal Pathophysiology, Institute of Natural Medicine, University of Toyama, Sugitani 2630, Toyama, 9300194, Japan

    Makoto Kadowaki

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  1. Li-Hua Wu
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  2. Peng Li
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  3. Qing-Li Zhao
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Correspondence to Qing-Li Zhao or Yu-Fei Jiao.

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Li-Hua Wu and Peng Li these authors have contributed equally to this study.

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Wu, LH., Li, P., Zhao, QL. et al. Arbutin, an intracellular hydroxyl radical scavenger, protects radiation-induced apoptosis in human lymphoma U937 cells. Apoptosis 19, 1654–1663 (2014). https://doi.org/10.1007/s10495-014-1032-x

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  • DOI: https://doi.org/10.1007/s10495-014-1032-x

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