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

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.

• Authors: Peng Zhang, Hong Li, Mo-Li Wu, Xiao-Yan Chen, Qing-You Kong, Xiao-Wei Wang, Yuan Sun, Shu Wen, Jia Liu
• Journal: Journal of neuro-oncology (J Neurooncol) Vol. 80 Issue 2 Pg. 123-31 (Nov 2006) ISSN: 0167-594X [Print] United States
• PMID: 16724266 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antioxidants
• Neoplasm Proteins
• Oligonucleotides, Antisense
• RNA, Neoplasm
• Stilbenes
• Resveratrol

Topics

• Antioxidants (pharmacology)
• Apoptosis (drug effects)
• Blotting, Western
• Brain Neoplasms (pathology)
• Cell Cycle (drug effects)
• Cell Line, Tumor
• Cell Survival (drug effects)
• Down-Regulation (drug effects)
• Flow Cytometry
• Fluorescent Antibody Technique
• Genes, myc (genetics)
• Humans
• Immunohistochemistry
• Medulloblastoma (pathology)
• Neoplasm Proteins (biosynthesis)
• Oligonucleotides, Antisense (genetics)
• RNA, Neoplasm (biosynthesis, genetics)
• Resveratrol
• Reverse Transcriptase Polymerase Chain Reaction
• S Phase (physiology)
• Stilbenes (pharmacology)
• Transfection