Gadolinium promoted proliferation and enhanced survival in human cervical carcinoma cells

Zhang, Ying; Fu, Lijuan; Li, Jinxia; Yang, Xiaoda; Wang, Kui

doi:10.1007/s10534-009-9208-5

Cited by 30 publications

(11 citation statements)

References 33 publications

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“…Several studies have described qualitatively similar but quantitatively different responses to individual lanthanoids. For example, variation has been reported in regard to protein stabilization in aqueous solution [47], reduction in lacunae formation by osteoclasts [48], and growth modulation in certain mammalian cell lines [14-16]. Other than to note differences among the elements for modulating one cell function or another, there is little that points to a particular chemical property as being critical.…”

Section: Discussionmentioning

confidence: 99%

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Fibroblast Response to Lanthanoid Metal Ion Stimulation: Potential Contribution to Fibrotic Tissue Injury

Jenkins

Perone

Walker

et al. 2011

Biol Trace Elem Res

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The purpose of this study was to compare each of the 14 naturally occurring lanthanoid metal ions for ability to stimulate pro-fibrotic responses in human dermal fibroblasts. When fibroblasts were exposed to individual lanthanoids over the concentration range of 1–100 μM, increased proliferation was observed with each of the agents as compared with control cells that were already proliferating rapidly in a growth factor-enriched culture medium. Dose-response differences were observed among the individual metal ions. Matrix metalloproteinase-1 (MMP-1) and tissue inhibitor of metalloproteinase-1 levels were also increased in response to lanthanoid exposure but type I procollagen production was not. A dose–response relationship between induction of proliferation and increased MMP-1 was observed. Non-lanthanoid transition metal ions (aluminum, copper, cobalt, iron, magnesium, manganese, nickel, and zinc) were examined in the same assays; there was little stimulation with any of these metals. When epidermal keratinocytes were examined in place of dermal fibroblasts, there was no growth stimulation with any of the lanthanoids. Several of the lanthanoid metals inhibited keratinocyte proliferation at higher concentrations (50–100 μM).

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Section: Discussionmentioning

confidence: 99%

“…Epithelial growth reduction is not universal, however, as increased proliferation and decreased differentiation have also been reported [14, 15]. Lanthanoid-induced growth arrest has also been seen with melanoma cells [16], but the underlying molecular mechanism is not known.…”

Section: Introductionmentioning

confidence: 99%

Fibroblast Response to Lanthanoid Metal Ion Stimulation: Potential Contribution to Fibrotic Tissue Injury

Jenkins

Perone

Walker

et al. 2011

Biol Trace Elem Res

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“…Gadolinium salts are known to inhibit the function of the mononuclear phagocytic system, and have an anticoagulant effect by inhibiting clotting reactions that require calcium (Lee et al 2004;Liao et al 2009). The effects of gadolinium salts on the proliferation and apoptosis of some normal and cancer cells have also been studied extensively (Sato et al 1998;Liu et al 2006;Fu et al 2009;Zhang et al 2009), and these effects related to cell proliferation and apoptosis depend on the concentrations or the types of cells being studied. This suggests that Gd-based treatments have potentials in medical applications in effective therapy of some diseases like cardiac disorders and cancers, and growing interest in the study on the mechanisms of Gd-induced biological effect on cell growth has been aroused.…”

Section: Introductionmentioning

confidence: 99%

“…This method with enhanced mass resolution, mass accuracy, and detection sensitivity, would allow to investigate the role of metabolites and relevant metabolic processes in different states. Previous study has demonstrated that GdCl 3 could inhibit or promote proliferation of several types of cancer cells lines including Hela cells, depending on the concentrations applied (Liu et al 2006;Zhang et al 2009). However, the underlying mechanism involved is poorly understood.…”

Section: Introductionmentioning

confidence: 99%

Metabolomic profiles delineate potential roles for gadolinium chloride in the proliferation or inhibition of Hela cells

et al. 2011

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Lanthanides (Lns) compounds have been reported to possess contrary effects on cell activity, i.e., promoting cell cycle progression and cell growth by lower concentration treatment, but suppressing cell proliferation and inducing cell apoptosis at higher dosing. However, the cellular processes during the intervention and the possible underlying mechanisms are still not well clarified. Using a combination of high-throughput liquid chromatography (LC) with mass spectrometry (MS), we have investigated the metabolomic profiles of Hela cells following gadolinium chloride (GdCl(3)) treatment in time- and concentration- dependent manners. A total of 48 metabolites released by Hela cells are identified to be differentially expressed (P < 0.05) in different states. Metabolic pathways analyses reveal that the differential metabolites are mainly characterized by increased lipid and amino acid metabolisms and by decreased lipid, amino acid, and carbohydrate metabolisms for cells treated with GdCl(3) at lower and higher concentrations, respectively. Notably, in the higher level GdCl(3) case, the down-expressions of metabolites are predominantly in the glycolytic and the redox pathways. The above results, obtained by using a metabolomic strategy for the first time, disclose that different cell signaling pathways are activated by GdCl(3) treatment with different concentrations, leading to inhibitory or promotional effect on Hela cells.

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“…Lanthanides (Ln) have been shown to promote cell proliferation and induce apoptosis depending on Ln species, concentrations and cell types. Most studies have shown that the proapoptosis effect appeared at the concentration higher up to millimolar levels, while proliferative effect often occured at micromolar concentration (Zhang et al 2009). However, recently some lanthanum (III) complexes have been synthesized with diverse ligands including chrysin (Zeng et al 2003), phenanthroline derivatives (Wang et al 2000(Wang et al , 2002Heffeter et al 2006) and coumarin derivatives (Kostova et al , 2006.…”

Section: Introductionmentioning

confidence: 99%

Proteomic analysis of lanthanum citrate-induced apoptosis in human cervical carcinoma SiHa cells

et al. 2010

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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.

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Gadolinium promoted proliferation and enhanced survival in human cervical carcinoma cells

Cited by 30 publications

References 33 publications

Fibroblast Response to Lanthanoid Metal Ion Stimulation: Potential Contribution to Fibrotic Tissue Injury

Fibroblast Response to Lanthanoid Metal Ion Stimulation: Potential Contribution to Fibrotic Tissue Injury

Metabolomic profiles delineate potential roles for gadolinium chloride in the proliferation or inhibition of Hela cells

Proteomic analysis of lanthanum citrate-induced apoptosis in human cervical carcinoma SiHa cells

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