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A potential role for resveratrol as a radiation sensitizer for melanoma treatment

  • Yujiang Fang
    Correspondence
    Corresponding authors. Department of Surgery, Ellis Fischel Cancer Center, University of Missouri School of Medicine, M316, Medical Sciences Building, Columbia, MO 65212. Tel.: +1 573 882 8454; fax: +1 573 884 6054. or Department of Surgery, Ellis Fischel Cancer Center, University of Missouri School of Medicine, M316, Medical Sciences Building, Columbia, MO 65212. Tel.: +1 573 882 8454; fax: +1 573 884 6054.
    Affiliations
    Department of Surgery, University of Missouri School of Medicine, Columbia, Missouri

    Ellis Fischel Cancer Center, University of Missouri School of Medicine, Columbia, Missouri
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  • Moore J. Bradley
    Affiliations
    Department of Surgery, University of Missouri School of Medicine, Columbia, Missouri
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  • Kathryn M. Cook
    Affiliations
    Department of Surgery, University of Missouri School of Medicine, Columbia, Missouri
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  • Elizabeth J. Herrick
    Affiliations
    Department of Surgery, University of Missouri School of Medicine, Columbia, Missouri
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  • Michael B. Nicholl
    Correspondence
    Corresponding authors. Department of Surgery, Ellis Fischel Cancer Center, University of Missouri School of Medicine, M316, Medical Sciences Building, Columbia, MO 65212. Tel.: +1 573 882 8454; fax: +1 573 884 6054. or Department of Surgery, Ellis Fischel Cancer Center, University of Missouri School of Medicine, M316, Medical Sciences Building, Columbia, MO 65212. Tel.: +1 573 882 8454; fax: +1 573 884 6054.
    Affiliations
    Department of Surgery, University of Missouri School of Medicine, Columbia, Missouri

    Ellis Fischel Cancer Center, University of Missouri School of Medicine, Columbia, Missouri
    Search for articles by this author
Published:March 15, 2013DOI:https://doi.org/10.1016/j.jss.2013.02.037

      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.

      Material and 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.

      Conclusion

      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.

      Keywords

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