Investigation of the anti-angiogenesis effects induced by deoxypodophyllotoxin-5-FU conjugate C069 against HUVE cells

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• 作者：Rong Xiang^a ; ^{xiangr04@qq.com} ; Xiao-Wen Guan^b ; Ling Hui^c ; Yong-Xin Jin^a ; Shi-Wu Chen^b ; ^{chenshw@lzu.edu.cn}
• 关键词：Podophyllotoxin ; 5-Fluorouracil ; Migration ; Angiogenesis ; Vascular disrupting effects
• 刊名：Bioorganic & Medicinal Chemistry Letters
• 出版年：2017
• 出版时间：15 February 2017
• 年：2017
• 卷：27
• 期：4
• 页码：713-717
• 全文大小：1326 K
• 卷排序：27

文摘

We have found that the deoxypodophyllotoxin-5-fluorouracil conjugate, 4′-O-demethyl-4-deoxyppodophyllotoxin-4′-yl 4-((6-(2-(5-fluorouracil-yl)acetamido) hexyl)amino)-4-oxobutanoate (C069), possessed superior cytotoxicities and less toxicity compared with etoposide. In this paper, the anti-angiogenic and vascular disrupting activities of C069 were examined with several in vitro and in vivo models. First, we demonstrated that C069 significantly inhibited the proliferation, migration, tube formation and disrupted the formed tube-like structures of HUVE cells, and inhibited angiogenesis in chicken chorioallantoic membrane assay. Furthermore, we found that C069 inhibited tube formation of HUVE cells by down-regulating the MMP-2, MMP-9, and phosphorylation of Akt and β-catenin. These results provided the initial evidence that C069 exerts potent anti-angiogenic and vascular disrupting effects.