PDZ-binding kinase/T-LAK cell-originated protein kinase is a target of the fucoidan from brown alga Fucus evanescens in the prevention of EGF-induced neoplastic cell transformation and colon cancer growth.
PDZ-binding kinase/T-LAK cell-originated protein kinase is a target of the fucoidan from brown alga Fucus evanescens in the prevention of EGF-induced neoplastic cell transformation and colon cancer growth.
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PDZ 结合激酶/T-LAK 细胞源性蛋白激酶是来自褐藻 Fucus evanescens 的岩藻依聚糖的靶标，可预防 EGF 诱导的肿瘤细胞转化和结肠癌生长
DOI：
10.18632/oncotarget.7708
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发表时间：
2016-04-05
期刊：
影响因子：
--
通讯作者：
Zhu F
中科院分区：
文献类型：
--
作者：
Vishchuk OS;Sun H;Wang Z;Ermakova SP;Xiao J;Lu T;Xue P;Zvyagintseva TN;Xiong H;Shao C;Yan W;Duan Q;Zhu F
从棕色墨角藻中分离得到一种具有较高抗癌活性的褐藻糖胶。该化合物通过抑制TOPK/ERK 1/2/MSK 1信号轴有效地防止EGF诱导的肿瘤细胞转化。体外研究表明，岩藻依聚糖硫酸酯在不同TOPK表达水平的结肠癌细胞中减弱丝裂原活化蛋白激酶下游信号传导，导致生长抑制。岩藻依聚糖通过在体外和离体直接与TOPK激酶相互作用并抑制其激酶活性来发挥其作用。在异种移植动物模型中，口服岩藻依聚糖抑制HCT 116结肠肿瘤生长。岩藻依聚糖还抑制肿瘤组织中TOPK下游信号分子的磷酸化。总之，我们的研究结果支持岩藻依聚糖通过其靶向TOPK在体外和离体预防肿瘤细胞转化和结肠癌进展的癌症预防功效。
The fucoidan with high anticancer activity was isolated from brown alga Fucus evanescens. The compound effectively prevented EGF-induced neoplastic cell transformation through inhibition of TOPK/ERK1/2/MSK 1 signaling axis. In vitro studies showed that the fucoidan attenuated mitogen-activated protein kinases downstream signaling in a colon cancer cells with different expression level of TOPK, resulting in growth inhibition. The fucoidan exerts its effects by directly interacting with TOPK kinase in vitro and ex vivo and inhibits its kinase activity. In xenograft animal model, oral administration of the fucoidan suppressed HCT 116 colon tumor growth. The phosphorylation of TOPK downstream signaling molecules in tumor tissues was also inhibited by the fucoidan. Taken together, our findings support the cancer preventive efficacy of the fucoidan through its targeting of TOPK for the prevention of neoplastic cell transformation and progression of colon carcinomas in vitro and ex vivo.