title: Combination of quercetin with radiotherapy enhances tumor radiosensitivity in vitro and in vivo.
abstract: OBJECTIVE
  Quercetin (3, 3,' 4', 5, 7 - five-flavonoids) is one of the main components of flavonoids, with multifunctions on immune function, anti-oxidation, anti-viral, anti-inflammatory, and cardiovascular protection. We hypothesize that a combination of quercetin with radiation would increase tumor radiosensitivity. To test this hypothesis, we conducted in vitro and in vivo studies.
  
  
  METHODS
  The in vitro radio-sensitization activity of quercetin was tested in DLD1, HeLa and MCF-7 tumor cell lines by colony formation assays. The in vivo activity was assessed in the DLD-1 human colorectal cancer xenograft model in nude mice. Mechanistic studies were conducted in several cell lines using Western blot analysis and immunofluorescence microscopy.
  
  
  RESULTS
  We found that quercetin can significantly increase tumor radiosensitivity both in vitro and in vivo. The in vitro Sensitizing Enhancement Ratios in DLD1, HeLa and MCF-7 cells were 1.87, 1.65, and 1.74, respectively. The mean doubling time of tumor xenografts was significantly increased in irradiated mice treated with quercetin. At the cellular level, exposure to quercetin resulted in prolonged DNA repair. The mechanistic studies demonstrated that quercetin induced radio-sensitization is through inhibiting the ATM kinase, one of the critical DNA damage response proteins.
  
  
  CONCLUSIONS
  We demonstrate both in vitro and in vivo evidence that combination of quercetin with radiotherapy can enhance tumor radiosensitivity by targeting the ATM-mediated pathway in response to radiation.
authors: Department of Nuclear Medicine, Jilin University, Changchun, China. chenghe.lin@yahoo.com
authors: Chenghe
authors: C
authors: Lin
authors: Yan
authors: Y
authors: Yu
authors: Hong-Guan
authors: HG
authors: Zhao
authors: Aimin
authors: A
authors: Yang
authors: Hong
authors: H
authors: Yan
authors: Yali
authors: Y
authors: Cui
mesh_terms: D000818:Animals; D064007:Ataxia Telangiectasia Mutated Proteins; D018797:Cell Cycle Proteins / Q000037:antagonists & inhibitors; D045744:Cell Line, Tumor; D004268:DNA-Binding Proteins / Q000037:antagonists & inhibitors; D006657:Histones / Q000032:analysis; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000032:analysis; D008297:Male; D051379:Mice; D009369:Neoplasms / Q000532:radiotherapy*; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors; D011794:Quercetin / Q000494:pharmacology*; D011836:Radiation Tolerance; D011838:Radiation-Sensitizing Agents / Q000494:pharmacology*; D025521:Tumor Suppressor Proteins / Q000037:antagonists & inhibitors; D000071857:Tumor Suppressor p53-Binding Protein 1
chemical_list: D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; C468783:H2AX protein, human; D006657:Histones; D047908:Intracellular Signaling Peptides and Proteins; D011838:Radiation-Sensitizing Agents; C498301:TP53BP1 protein, human; D025521:Tumor Suppressor Proteins; D000071857:Tumor Suppressor p53-Binding Protein 1; D011794:Quercetin; C576324:ATM protein, human; D064007:Ataxia Telangiectasia Mutated Proteins; C576325:Atm protein, mouse; D017346:Protein Serine-Threonine Kinases