Radiation induced fibrosis of the skin is a late toxicity that may result in loss of function due to reduced range of motion and pain. The current study sought to determine if oral delivery of quercetin mitigates radiation-induced cutaneous injury. Female C3H/HeN mice were fed control chow or quercetin-formulated chow (1% by weight). The right hind leg was exposed to 35 Gy of X rays and the mice were followed serially to assess acute toxicity and hind leg extension. Tissue samples were collected for assessment of soluble collagen and tissue cytokines. Human and murine fibroblasts were subjected to clonogenic assays to determine the effects of quercetin on radiation response. Contractility of fibroblasts was assessed with a collagen contraction assay in the presence or absence of quercetin and transforming growth factor-β (TGF-β). Western blotting of proteins involved in fibroblast contractility and TGF-β signaling were performed. Quercetin treatment significantly reduced hind limb contracture, collagen accumulation and expression of TGF-β in irradiated skin. Quercetin had no effect on the radioresponse of fibroblasts or murine tumors, but was capable of reducing the contractility of fibroblasts in response to TGF-β, an effect that correlated with partial stabilization of phosphorylated cofilin. Quercetin is capable of mitigating radiation induced skin fibrosis and should be further explored as a therapy for radiation fibrosis.
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1 August 2013
REGULAR ARTICLES|
July 02 2013
Quercetin Inhibits Radiation-Induced Skin Fibrosis
Jason A. Horton;
Jason A. Horton
aRadiation Oncology Branch, National Cancer Institute, Bethesda, Maryland 20892
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Fei Li;
Fei Li
bLaboratory of Metabolism, National Cancer Institute, Bethesda, Maryland 20892
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Eun Joo Chung;
Eun Joo Chung
aRadiation Oncology Branch, National Cancer Institute, Bethesda, Maryland 20892
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Kathryn Hudak;
Kathryn Hudak
aRadiation Oncology Branch, National Cancer Institute, Bethesda, Maryland 20892
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Ayla White;
Ayla White
aRadiation Oncology Branch, National Cancer Institute, Bethesda, Maryland 20892
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Kristopher Krausz;
Kristopher Krausz
bLaboratory of Metabolism, National Cancer Institute, Bethesda, Maryland 20892
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Frank Gonzalez;
Frank Gonzalez
bLaboratory of Metabolism, National Cancer Institute, Bethesda, Maryland 20892
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Deborah Citrin
Deborah Citrin
1
aRadiation Oncology Branch, National Cancer Institute, Bethesda, Maryland 20892
1Address for correspondence: Radiation Oncology Branch, CCR, National Cancer Institute, 10-CRC-Hatfield Clinical Research Center, B2-3500, Bethesda, MD 20892-1682; e-mail: [email protected].
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Radiat Res (2013) 180 (2): 205–215.
Citation
Jason A. Horton, Fei Li, Eun Joo Chung, Kathryn Hudak, Ayla White, Kristopher Krausz, Frank Gonzalez, Deborah Citrin; Quercetin Inhibits Radiation-Induced Skin Fibrosis. Radiat Res 1 August 2013; 180 (2): 205–215. doi: https://doi.org/10.1667/RR3237.1
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