Novel bile acid derivatives induce apoptosis via a p53-independent pathway in human breast carcinoma cells
Novel bile acid derivatives induce apoptosis via a p53-independent pathway in human breast carcinoma cells
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DOI：
10.1016/s0304-3835(00)00671-6
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发表时间：
2001-02-10
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, EO;Choi, YH;Kim, ND
比较了熊去氧胆酸(UDCA)、鹅去氧胆酸(CDCA)及其衍生物HS-1183、HS-1199和HS-1200对野生型p53细胞MCF-7和突变型p53细胞MDA-MB-231的抑制作用。而UDCA和CDCA没有明显的作用，它们的新衍生物以浓度依赖的方式抑制这两种细胞的增殖，伴随着凋亡的核变化、亚G1期群体的增加和DNA片段化。此外，在MCF-7和MDA-MB-231细胞中，黑麦还观察到促凋亡蛋白Bax/抗凋亡蛋白Bcl2的比值增加以及层蛋白B和多聚ADP核糖聚合酶(PARP)的裂解。经新型胆汁酸处理后，细胞周期相关蛋白Cyclin D1、D3和视网膜母细胞瘤蛋白(PRB)表达下调，而细胞周期蛋白依赖性激酶抑制因子p21(WAF1/CIP1)表达上调。这些发现表明，新的胆酸衍生物对人乳腺癌细胞的这些细胞毒性作用是通过P53非依赖的途径通过凋亡来介导的。(C)2001爱思唯尔爱尔兰科学有限公司。保留所有权利。
We have compared the anti-proliferative effects of ursodeoxycholic acid (UDCA), chenodeoxycholic acid (CDCA) and their derivatives, HS-1183, HS-1199 and HS-1200, on MCF-7 (wild-type p53) and MDA-MB-231 (mutant p53) cells. While UDCA and CDCA exhibited no significant effect, their novel derivatives inhibited the proliferation of both cell lines in a concentration-dependent manner, concomitant with apoptotic nuclear changes and the increase of a sub-G1 population and DNA fragmentation. Furthermore, rye also observed an increase in the ratio of pro-apoptotic protein Bax to anti-apoptotic protein Bcl-2 and cleavages of lamin B and poly(ADP-ribose) polymerase (PARP) in MCF-7 and MDA-MB-231 cells. Cell cycle related proteins, cyclin D1 and D3, as well as retinoblastoma protein (pRb) were down-regulated, while the level of cyclin-dependent kinase inhibitor p21(WAF1/CIP1) was increased in both cancer cells after treatment with novel bile acids. These findings suggest that these cytotoxic effects of novel bile acid derivatives on human breast carcinoma cells were mediated via apoptosis through a p53-independent pathway. (C) 2001 Elsevier Science ireland Ltd. All rights reserved.