title: Halofuginone enhances the radiation sensitivity of human tumor cell lines.
abstract: Transforming growth factor beta (TGF-beta) is implicated in radiation-induced fibrosis of normal tissues in patients receiving radiotherapy. Inhibiting the TGF-beta 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-beta 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-beta receptor II protein levels, leading to increased cellular radiosensitization. These data further support the goal of manipulating the TGF-beta pathway to achieve a positive increase in the therapeutic gain in clinical radiotherapy.
authors.affiliation: Radiation Biology Branch, Center for Cancer Research, National Cancer Institute, Bethesda, MD 20892-1002, USA.
authors.forename: John A
authors.initials: JA
authors.lastname: Cook
authors.forename: Rajani
authors.initials: R
authors.lastname: Choudhuri
authors.forename: William
authors.initials: W
authors.lastname: Degraff
authors.forename: Janet
authors.initials: J
authors.lastname: Gamson
authors.forename: James B
authors.initials: JB
authors.lastname: Mitchell
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D015153:Blotting, Western; D045744:Cell Line, Tumor; D002470:Cell Survival; D005434:Flow Cytometry; D006801:Humans; D010880:Piperidines / Q000494:pharmacology*; D052999:Quinazolinones / Q000494:pharmacology*; D011836:Radiation Tolerance / Q000187:drug effects*; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D000970:Antineoplastic Agents; D010880:Piperidines; D052999:Quinazolinones; C010176:halofuginone