Ursodeoxycholic acid (UDCA) can inhibit deoxycholic acid (DCA)-induced apoptosis via modulation of EGFR/Raf-1/ERK signaling in human colon cancer cells
Ursodeoxycholic acid (UDCA) can inhibit deoxycholic acid (DCA)-induced apoptosis via modulation of EGFR/Raf-1/ERK signaling in human colon cancer cells
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DOI：
10.1093/jn/134.2.483
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发表时间：
2004-02-01
影响因子：
4.2
通讯作者：
Martinez, JD
中科院分区：
文献类型：
--
作者：
Im, E;Martinez, JD
熊去氧胆酸 (UDCA) 是一种亲水性胆汁酸，被称为细胞保护剂。 UDCA 可防止多种应激刺激诱导的细胞凋亡，包括细胞毒性胆汁酸，如脱氧胆酸 (DCA)。在这里，我们研究了 UDCA 拮抗 DCA 诱导的人结肠癌细胞凋亡的分子机制。 UDCA 预处理可减少因接触 DCA 和 UDCA 引起的凋亡细胞数量。信号通路的进一步研究表明，UDCA 预处理抑制了激活蛋白-1 的 DNA 结合活性，同时伴随着 DCA 刺激的细胞外信号调节激酶 (ERK) 和 Raf-1 激酶活性的下调。 DCA 还被发现可以激活表皮生长因子受体 (EGFR) 活性，而 UDCA 可以抑制这种活性。总的来说，这些发现表明 UDCA 对 DCA 诱导的细胞凋亡的抑制作用部分是通过 EGFR/Raf-1/ERK 信号传导的调节介导的。
Ursodeoxycholic acid (UDCA), a hydrophilic bile acid, is known as a cytoprotective agent. UDCA prevents apoptosis induced by a variety of stress stimuli including cytotoxic bile acids such as deoxycholic acid (DCA). Here we examined the molecular mechanism by which UDCA can antagonize DCA-induced apoptosis in human colon cancer cells. UDCA pretreatment decreases the number of apoptotic cells caused by exposure to DCA and UDCA. Further studies of the signaling pathway showed that UDCA pretreatment suppressed DNA binding activity of activator protein-1 and this was accompanied by downregulation of both extracellular signal-regulated kinase (ERK) and Raf-1 kinase activities stimulated by exposure to DCA. DCA was also found to activate epidermal growth factor receptor (EGFR) activity and UDCA inhibited this. Collectively, these findings suggest that the inhibitory effect of UDCA in DCA-induced apoptosis is partly mediated by modulation of EGFR/Raf-1/ERK signaling.