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

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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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Acknowledgement

This work is supported in part by grants from the National Natural Science Foundation of China (30370448 and 30527002), the National Department of Traditional Chinese Medicine (2000-J-P-26) and the Dalian Bureau for Science and Technology, China.

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Authors and Affiliations

  1. Cancer Institute and Liaoning Laboratory of Cancer Genomics, College of Basic Medical Sciences, Dalian Medical University, 116027, Dalian, P. R. China

    Peng Zhang, Hong Li, Mo-Li Wu, Xiao-Yan Chen, Qing-You Kong, Xiao-Wei Wang, Yuan Sun, Shu Wen & Jia Liu

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  1. Peng Zhang
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  2. Hong Li
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Correspondence to Jia Liu.

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Zhang, P., Li, H., Wu, ML. et al. c-Myc downregulation: a critical molecular event in resveratrol-induced cell cycle arrest and apoptosis of human medulloblastoma cells. J Neurooncol 80, 123–131 (2006). https://doi.org/10.1007/s11060-006-9172-7

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  • DOI: https://doi.org/10.1007/s11060-006-9172-7

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