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    c-Myc downregulation: a critical molecular event in resveratrol-induced cell cycle arrest and apoptosis of human medulloblastoma cells.

    • Authors:
    • Peng Zhang
      Center for Cancer and Immunology Research
      Houston | United States
      Hong Li
      Research Center for Brain Function and Psychological Science
      China
      Mo-Li Wu
      Dalian Medical University
      China
      Xiao-yan Chen
      Shanghai Institute of Materia Medica
      China
      Qing-You Kong
      Dalian Medical University
      China
      Xiao-Wei Wang
      Peking University School of Pharmaceutical Sciences
      China
      Yuan Sun
      Harbin Veterinary Research Institute
      China
      Shu Wen
      Institute of Biosciences and Technology
      United States
      Jia Liu
      Institute of Basic Research in Clinical Medicine
      China
    J Neurooncol 2006 Nov 25;80(2):123-31. Epub 2006 May 25.
    Cancer Institute and Liaoning Laboratory of Cancer Genomics, College of Basic Medical Sciences, Dalian Medical University, 116027, Dalian, P. R. China.
    The correlation of c-Myc expression with resveratrol-induced turnover of medulloblastoma cells was investigated in this study by checking (1) c-Myc expression in medulloblastoma tissues and cell lines (UW228-2 and UW228-3), (2) the in vitro effect of resveratrol on c-Myc expression and (3) the influences of c-Myc inhibition in cell growth and survival. Immunohistochemical staining of human medulloblastomas and noncancerous cerebellar tissues revealed that 8 out of 11 tumor tissues (72.7%) expressed c-Myc, in which 4 cases (50%) showed intensified nuclear labeling. RT-PCR, Western blotting, immunocytochemical and immunofluorescence stainings revealed c-Myc downregulation accompanied with growth suppression and apoptosis. Flow cytometry analysis showed S phase arrest in resveratrol-treated cell populations. Transfection of c-Myc directed antisense oligonucleotides to the cultured medulloblastoma cells could reduce c-Myc expression, inhibit cell growth and arrest the cell cycle at S phase. Our results thus for the first time demonstrate that c-Myc downregulation is a critical molecular event of resveratrol-mediated anti-medulloblastoma activity, which is closely associated with growth suppression, cell cycle arrest and apoptosis of medulloblastoma cells.
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