Lanthanides possess diverse
biological effect and have been shown to promote cell proliferation and induce apoptosis. Our previous studies showing that
lanthanide citrate complex has significant antitumor activity in human
cervical cancer HeLa cells. This study aims at determining if [LaCit(2)](3-) have the activity against another type of human
cervical cancer cell line SiHa and the changes in
protein expression that contribute to the mechanism(s) of [LaCit(2)](3-)-mediated apoptosis in SiHa cells. Cell growth inhibition was measured by MTT method, and apoptosis was detected by means of
Hoechst 33258 staining and flow cytometry analysis. After [LaCit(2)](3-)-treatment the results show that the growth of SiHa cells was inhibited, the cells displayed typical apoptosis morphological changes, and increase in the rates of apoptosis. Using proteomics approaches, a variety of differentially expressed
proteins were identified in SiHa cells before and
after treatment with [LaCit(2)](3-). There were profound changes in 10
proteins relating to mitochondrial function and oxidative stress, suggesting that
mitochondrial dysfunction plays a key role in [LaCit(2)](3-)-induced apoptosis. This was confirmed by a decrease in the mitochondrial transmembrane potential (Δψ(m)), and increases in H(2)O(2) generation in [LaCit(2)](3-)-treated cells. Among them the alerted
proteins, Prx I, ANXA1 and
TRAF5 were validated by western blotting analyses. These results suggest that there is an intrinsic molecular pathway of cell apoptosis in [LaCit(2)](3-)-treated SiHa cells. This observation is in accordance with our previous reports about the effects of [LaCit(2)](3-) and [YbCit(2)](3-) on HeLa cells and it provide a molecular mechanism underlying
lanthanide citrate complex-mediated cell apoptosis.