Zebularine-induced reduction in VEGF secretion by HIF-1α degradation in oral squamous cell carcinoma

Maiko Suzuki, Fumiaki Shinohara, Hidemi Rikiishi

研究成果: Article査読

12 被引用数 (Scopus)


Vascular endothelial growth factor (VEGF) is a potent inducer of angiogenesis in oral squamous cell carcinoma (OSCC). In this study, we used the novel DNA methyltransferase inhibitor zebularine (Zeb) to investigate epigenetic influences on the secretion of VEGF-A in the OSCC cell line HSC-3. Under normoxic conditions, we found that Zeb inhibited secretion in a dose-dependent manner by reducing the activity of hypoxia-inducible factor-1α (HIF-1α). Treatment of the cells with the proteasome inhibitor MG132 protected the HIF-1α protein from Zeb-mediated epigenetic regulation. In addition, our study revealed that neither the PI3K/Akt nor the p53 signaling pathway is required for Zeb-induced HIF-1α degradation. In short, Zeb influenced the stability of the HIF-1α protein and the activity of its targets, such as VEGF, in HSC-3 cells in normoxic conditions. This study has laid the foundation for a novel anti-cancer approach, which may find applications in molecular staging.

ジャーナルMolecular medicine reports
出版ステータスPublished - 2008

ASJC Scopus subject areas

  • 生化学
  • 分子医療
  • 分子生物学
  • 遺伝学
  • 腫瘍学
  • 癌研究


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