Shen Liming, Liu Qiong, Ni Jiazuan, Hong Guangyan
College of Life Sciences, Shenzhen University, Nanhai Road #3688, Nanshan District, Shenzhen 518060, Guangdong Province, PR China.
Chem Biol Interact. 2009 Oct 30;181(3):455-62. doi: 10.1016/j.cbi.2009.07.013. Epub 2009 Jul 24.
Lanthanides have been reported to induce apoptosis in cancer cell lines. Human cervical cancer cell line HeLa was found to be more sensitive to dicitratolanthanum (III) complex (LaCit2) than other cancer cell lines. However, the effect and mechanism of dicitratoytterbium (III) complex (YbCit2) on HeLa cells is unknown. Using biochemical and comparative proteomic analyses, YbCit2 was found to inhibit HeLa cell growth and induce apoptosis. Similar to the effects of LaCit2, proteomics results from YbCit2-treated cells revealed profound changes in proteins relating to mitochondria and oxidative stress, suggesting that mitochondrial dysfunction plays a key role in YbCit2-induced apoptosis. This was confirmed by the decreased mitochondrial transmembrane potential and the increased generation of reactive oxygen species in YbCit2-treated cells. Western blot analysis showed that YbCit2-induced apoptosis was accompanied by the activation of caspase-9 and specific proteolytic cleavage of PARP, leading to an increase in the pro-apoptotic protein Bax and a decrease in the anti-apoptotic protein Bcl-2. These results suggest a mitochondrial pathway of cell apoptosis in YbCit2-treated cells, which will help us understand the molecular mechanisms of lanthanide-induced apoptosis in tumor cells.
据报道，镧系元素可诱导癌细胞系发生凋亡。人们发现人宫颈癌细胞系HeLa对柠檬酸镧（III）配合物（LaCit2）比其他癌细胞系更敏感。然而，柠檬酸镱（III）配合物（YbCit2）对HeLa细胞的作用及机制尚不清楚。通过生化和比较蛋白质组学分析，发现YbCit2可抑制HeLa细胞生长并诱导凋亡。与LaCit2的作用类似，YbCit2处理的细胞的蛋白质组学结果显示，与线粒体和氧化应激相关的蛋白质发生了深刻变化，这表明线粒体功能障碍在YbCit2诱导的凋亡中起关键作用。YbCit2处理的细胞中线粒体跨膜电位降低和活性氧生成增加证实了这一点。蛋白质印迹分析表明，YbCit2诱导的凋亡伴随着caspase-9的激活和PARP的特异性蛋白水解切割，导致促凋亡蛋白Bax增加，抗凋亡蛋白Bcl-2减少。这些结果表明了YbCit2处理的细胞中细胞凋亡的线粒体途径，这将有助于我们理解镧系元素诱导肿瘤细胞凋亡的分子机制。
