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

0301 basic medicine 0303 health sciences Brain Neoplasms Cell Survival Reverse Transcriptase Polymerase Chain Reaction Blotting, Western Cell Cycle Genes, myc Down-Regulation Fluorescent Antibody Technique Apoptosis Oligonucleotides, Antisense Flow Cytometry Immunohistochemistry Antioxidants Neoplasm Proteins S Phase 03 medical and health sciences Resveratrol Cell Line, Tumor Humans RNA, Neoplasm Medulloblastoma
DOI: 10.1007/s11060-006-9172-7 Publication Date: 2006-05-24T11:44:14Z
ABSTRACT
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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