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.
Zhang
Peng
P
Cancer Institute and Liaoning Laboratory of Cancer Genomics, College of Basic Medical Sciences, Dalian Medical University, 116027, Dalian, P. R. China.
Li
Hong
H
Wu
Mo-Li
ML
Chen
Xiao-Yan
XY
Kong
Qing-You
QY
Wang
Xiao-Wei
XW
Sun
Yuan
Y
Wen
Shu
S
Liu
Jia
J
D000975:Antioxidants / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D015153:Blotting, Western; D001932:Brain Neoplasms / Q000473:pathology*; D002453:Cell Cycle / Q000187:drug effects*; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D015536:Down-Regulation / Q000187:drug effects; D005434:Flow Cytometry; D005455:Fluorescent Antibody Technique; D016259:Genes, myc / Q000235:genetics*; D006801:Humans; D007150:Immunohistochemistry; D008527:Medulloblastoma / Q000473:pathology*; D009363:Neoplasm Proteins / Q000096:biosynthesis; D016376:Oligonucleotides, Antisense / Q000235:genetics; D012334:RNA, Neoplasm / Q000096:biosynthesis / Q000235:genetics; D000077185:Resveratrol; D020133:Reverse Transcriptase Polymerase Chain Reaction; D016196:S Phase / Q000502:physiology; D013267:Stilbenes / Q000494:pharmacology*; D014162:Transfection
D000975:Antioxidants; D009363:Neoplasm Proteins; D016376:Oligonucleotides, Antisense; D012334:RNA, Neoplasm; D013267:Stilbenes; D000077185:Resveratrol