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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Authors | Liming Shen, Qiong Liu, Jiazuan Ni, Guangyan Hong |
Journal | Chemico-biological interactions
(Chem Biol Interact)
Vol. 181
Issue 3
Pg. 455-62
(Oct 30 2009)
ISSN: 1872-7786 [Electronic] Ireland |
PMID | 19632212
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Citrates
- Neoplasm Proteins
- Organometallic Compounds
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Topics |
- Blotting, Western
- Citrates
(pharmacology)
- Electrophoresis, Gel, Two-Dimensional
- Female
- HeLa Cells
- Humans
- Neoplasm Proteins
(metabolism)
- Organometallic Compounds
(pharmacology)
- Oxidative Stress
- Proteomics
- Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
- Uterine Cervical Neoplasms
(metabolism, pathology)
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