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

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.