Halofuginone enhances the radiation sensitivity of human tumor cell lines |
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Authors: | John A. Cook Rajani ChoudhuriWilliam DeGraff Janet GamsonJames B. Mitchell |
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Affiliation: | Radiation Biology Branch, Center for Cancer Research, National Cancer Institute, Bethesda, MD 20892-1002, USA |
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Abstract: | Transforming growth factor beta (TGF-β) is implicated in radiation-induced fibrosis of normal tissues in patients receiving radiotherapy. Inhibiting the TGF-β signaling pathway by various means has been shown to reduce radiation-induced fibrosis in pre-clinical studies. The present study evaluated the effects of interfering with the TGF-β signaling pathway on the radiosensitivity of selected human tumor cell lines using the plant-derived alkaloid, halofuginone. Halofuginone treatment inhibited cell growth, halted cell cycle progression, decreased radiation-induced DNA damage repair, and decreased TGF-β receptor II protein levels, leading to increased cellular radiosensitization. These data further support the goal of manipulating the TGF-β pathway to achieve a positive increase in the therapeutic gain in clinical radiotherapy. |
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Keywords: | Radiation sensitizer TGF-beta Halofuginone Fibrosis |
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