title: A potential role for resveratrol as a radiation sensitizer for melanoma treatment.
abstract: BACKGROUND
  Radiotherapy (XRT) is used to improve local control of melanoma and for palliation of metastatic disease. Clinical use of XRT for melanoma is often limited by extent of disease and the relative radioresistance of melanoma may limit the effectiveness of XRT. Our group and others have previously shown that resveratrol (RSV) enhances radiation sensitivity in radioresistant prostate cancer cell lines.
  
  
  METHODS
  In this study, the effects of XRT in combination with RSV on radioresistant melanoma lines, SK-Mel-5 and HTB-65, were evaluated by assessment of proliferation and apoptosis. Clonogenic assay, comparison of proliferating cell nuclear antigen staining, Quick Cell Proliferation assay, terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) staining and caspase-3 activity assay were used to assess proliferation and apoptosis, as appropriate.
  
  
  RESULTS
  We found that the percentage of colonies, proliferating cell nuclear antigen + cells and the optical density value of melanoma cells were decreased after addition of RSV to XRT (XRT/RSV). TUNEL + cells and the relative caspase-3 activity in melanoma cells were increased after addition of RSV to XRT (XRT/RSV). We investigated the possible molecular mechanisms of decreased proliferation and increased apoptosis by using reverse transcriptase-polymerase chain reaction and immunohistochemical staining. The anti-proliferative effect of XRT/RSV correlated with decreased expression of pro-proliferative molecule cyclin B, cyclin D, cdk2 and cdk4. The pro-apoptotic effect of XRT/RSV correlated with decreased expression of the anti-apoptotic molecule FLIP, Bcl-2, and survivin.
  
  
  CONCLUSIONS
  These data suggest that RSV enhances radiation sensitivity of melanoma cells by inhibiting proliferation and promoting apoptosis. Resveratrol may have a potential role as a radiation sensitizer for melanoma treatment.
authors.affiliation: Department of Surgery, University of Missouri School of Medicine, Columbia, MO 65212, USA. fangy@health.missouri.edu
authors.forename: Yujiang
authors.initials: Y
authors.lastname: Fang
authors.forename: Moore J
authors.initials: MJ
authors.lastname: Bradley
authors.forename: Kathryn M
authors.initials: KM
authors.lastname: Cook
authors.forename: Elizabeth J
authors.initials: EJ
authors.lastname: Herrick
authors.forename: Michael B
authors.initials: MB
authors.lastname: Nicholl
mesh_terms: D000972:Antineoplastic Agents, Phytogenic / Q000627:therapeutic use*; D017209:Apoptosis / Q000187:drug effects / Q000528:radiation effects; D053148:Caspase 3 / Q000378:metabolism; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects / Q000528:radiation effects; D003131:Combined Modality Therapy; D056741:Cyclin D / Q000378:metabolism; D004358:Drug Therapy; D006801:Humans; D051034:Inhibitor of Apoptosis Proteins / Q000378:metabolism; D008545:Melanoma / Q000188:drug therapy* / Q000473:pathology / Q000532:radiotherapy*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D011838:Radiation-Sensitizing Agents / Q000627:therapeutic use*; D011878:Radiotherapy; D000077185:Resveratrol; D012878:Skin Neoplasms / Q000188:drug therapy* / Q000473:pathology / Q000532:radiotherapy*; D013267:Stilbenes / Q000627:therapeutic use*; D000077022:Survivin
chemical_list: D000972:Antineoplastic Agents, Phytogenic; C107489:BIRC5 protein, human; D056741:Cyclin D; D051034:Inhibitor of Apoptosis Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D011838:Radiation-Sensitizing Agents; D013267:Stilbenes; D000077022:Survivin; D053148:Caspase 3; D000077185:Resveratrol
keywords: Apoptosis; Proliferation; Radiation; Resveratrol