Synthetic bile acid derivatives induce apoptosis through a c-Jun N-terminal kinase and NF-κB-dependent process in human cervical carcinoma cells
Synthetic bile acid derivatives induce apoptosis through a c-Jun N-terminal kinase and NF-κB-dependent process in human cervical carcinoma cells
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DOI：
10.1016/j.canlet.2004.11.055
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发表时间：
2005-11-08
期刊：
影响因子：
9.7
通讯作者：
Kim, ND
中科院分区：
文献类型：
--
作者：
Im, E;Choi, SH;Kim, ND
最近，我们报道了熊去氧胆酸（UDCA）的合成衍生物HS-1183，鹅去氧胆酸（CDCA）的衍生物HS-1199和HS-1200，通过p53非依赖性途径诱导人乳腺癌细胞凋亡。在这里，我们提出的合成胆汁酸衍生物诱导SiHa人宫颈癌细胞凋亡以及。在检测的浓度范围内，母体化合物UDCA和CDCA对细胞活力无显著影响。然而，它们的合成胆汁酸衍生物以浓度依赖性方式显著降低细胞活力。细胞凋亡的特征表现，包括DNA片段化，促凋亡蛋白Bax的水平增加，和裂解的聚（ADP-核糖）聚合酶时，这些合成的化合物处理的细胞。核转录因子NF-κ B的核转位增加，这表明合成化合物以NF-κ B依赖性途径诱导细胞凋亡。p38和细胞外信号调节激酶的磷酸化不受影响，而c-Jun N-末端激酶（INK）随着转录因子c-Jun水平的增加而被沿着激活。我们的研究表明，新合成的胆汁酸能够通过激活INK和NF-κ B B来抑制SiHa细胞的增殖并诱导细胞凋亡。(C)2005爱思唯尔爱尔兰有限公司保留所有权利。
Recently, we have reported that a synthetic derivative of ursodeoxycholic acid (UDCA), HS-1183, and those of chenodeoxycholic acid (CDCA), HS-1199 and HS-1200, induced apoptosis in human breast carcinoma cells through a p53-independent pathway. Here, we present that the synthetic bile acid derivatives induce apoptosis in SiHa human cervical carcinoma cells as well. The parental compounds, UDCA and CDCA, exhibited no significant effect on the cell viability at the concentration ranges tested. However, their synthetic bile acid derivatives significantly decreased cell viability in a concentration dependent manner. Characteristic manifestations of apoptosis including DNA fragmentation, an increased level of proapoptotic protein Bax, and cleavage of poly(ADP-ribose) polymerase were shown when the cells were treated with these synthetic compounds. Nuclear translocation of nuclear transcription factor NF-kappa B was increased and this suggests that the synthetic compounds induce apoptosis in a NF-kappa B dependent pathway. Phosphorylations of p38 and extracellular signal-regulated kinase were not affected, whereas c-Jun N-terminal kinase (INK) was activated along with an increased level of transcription factor c-Jun. Our studies demonstrate that the newly synthesized bile acids are capable of inhibiting cell proliferation and inducing apoptosis in SiHa cells through activation of INK and NF-kappa B. (C) 2005 Elsevier Ireland Ltd. All rights reserved.