A proteomic investigation into the human cervical cancer cell line HeLa treated with dicitratoytterbium (III) complex |
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Authors: | Liming Shen Jiazuan Ni |
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Institution: | a College of Life Sciences, Shenzhen University, Nanhai Road #3688, Nanshan District, Shenzhen 518060, Guangdong Province, PR China b Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun 130022, PR China |
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Abstract: | 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]3−) than other cancer cell lines. However, the effect and mechanism of dicitratoytterbium (III) complex (YbCit2]3−) on HeLa cells is unknown. Using biochemical and comparative proteomic analyses, YbCit2]3− was found to inhibit HeLa cell growth and induce apoptosis. Similar to the effects of LaCit2]3−, proteomics results from YbCit2]3−-treated cells revealed profound changes in proteins relating to mitochondria and oxidative stress, suggesting that mitochondrial dysfunction plays a key role in YbCit2]3−-induced apoptosis. This was confirmed by the decreased mitochondrial transmembrane potential and the increased generation of reactive oxygen species in YbCit2]3−-treated cells. Western blot analysis showed that YbCit2]3−-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]3−-treated cells, which will help us understand the molecular mechanisms of lanthanide-induced apoptosis in tumor cells. |
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Keywords: | GAPDH glyceraldehyde 3-phosphate dehydrogenase HPV human papillomavirus MTT 3-(4 5-dimethylthiazol-2-yl)-2 5-diphenyltetrazoliumbromide JC-1 5&prime 6 6&prime -tetrachloro-1 1&prime 3 3&prime -tetraethylbenzimidazolcarbo-cyanineiodide PTP permeability transition pore ROS reactive oxygen species Δψm mitochondrial transmembrane potential DCFH-DA 2&prime 7&prime -dichlorofluorescein VDAC voltage-dependent anion-selective channel SOD1 copper zinc superoxide dismutase 1 PHB prohibitin PARP poly ADP-ribose polymerase eIF3i eukaryotic translation initiation factor 3 subunit 2 QPRTase quinolinate phosphoribosyltransferase VDAC voltage-dependent anion-selective channel eEF2 eukaryotic translation elongation factor 2 DTT DL-dithiothreitol |
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