A Redox-Silent Analogue of Tocotrienol Inhibits Cobalt(Ⅱ) Chloride-Induced VEGF Expression via Yes Signaling in Mesothelioma Cells

DOI Web Site Web Site PubMed 被引用文献3件

書誌事項

タイトル別名
  • A Redox-Silent Analogue of Tocotrienol Inhibits Cobalt(II) Chloride-Induced VEGF Expression <i>via</i> Yes Signaling in Mesothelioma Cells

この論文をさがす

抄録

Vascular endothelial growth factor (VEGF) plays a crucial role in tumor angiogenesis and represents an attractive anticancer target. We have previously demonstrated that a redox-silent analogue of α-tocotrienol, 6-O-carboxypropyl-α-tocotrienol (T3E) exhibits potent anti-carcinogenic property in human malignant mesothelioma (MM) cells. However, inhibition of tumor growth by targeting VEGF pathway remains undetermined. In this study, we explored the inhibitory effect of T3E on the paracrine secretion of VEGF in MM cells under mimicked hypoxia by cobalt chloride (CoCl2). In this study we examine whether T3E can suppress the secretion of VEGF in MM cells exposed to mimic hypoxia by cobalt chloride (CoCl2). We found that CoCl2-induced hypoxia treatment leads to increased up-regulated hypoxia-inducible factor-2α (HIF-2α) and subsequently induced the secretion of VEGF in MM cells. This up-regulation activation mainly depended on the activation of Yes, a member of the Src family of kinases. Treatment of hypoxic MM cells with T3E effectively inhibited the secretion of VEGF, On the other hand, T3E inhibited CoCl2-induced gene expression of VEGF due to the inactivation of Yes/HIF-2α signaling. These data suggest that Yes/HIF2-α/VEGF could be a promising therapeutic target of T3E in MM cells.

収録刊行物

被引用文献 (3)*注記

もっと見る

キーワード

詳細情報 詳細情報について

問題の指摘

ページトップへ