Fluoride induces apoptosis by caspase-3 activation in human leukemia HL-60 cells

Anuradha, C. D.; Kanno, Sanse; Hirano, Seishiro

doi:10.1007/s002040000132

Cited by 64 publications

(31 citation statements)

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“…Several studies have shown that millimolar levels of F can induce apoptosis in many cell types, including hepatic cells, epithelial lung cells, human leukemia HL-60 cells, and ameloblast-lineage cells. [27][28][29][30] We have also shown that F increases apoptosis in hippocampal and osteoblast-like cells. 10 However, other mechanisms can be involved in F-mediated cell death, such as endoplasmic reticulum stress.…”

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confidence: 67%

Pharmacological and toxicological effects of co-exposure of human gingival fibroblasts to silver nanoparticles and sodium fluoride

Inkielewicz‐Stępniak¹,

Santos-Martínez²,

Medina³

et al. 2014

IJN

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Background Silver nanoparticles (AgNPs) and fluoride (F) are pharmacological agents widely used in oral medicine and dental practice due to their anti-microbial/anti-cavity properties. However, risks associated with the co-exposure of local cells and tissues to these xenobiotics are not clear. Therefore, we have evaluated the effects of AgNPs and F co-exposure on human gingival fibroblast cells. Methods Human gingival fibroblast cells (CRL-2014) were exposed to AgNPs and/or F at different concentrations for up to 24 hours. Cellular uptake of AgNPs was examined by transmission electron microscopy. Downstream inflammatory effects and oxidative stress were measured by real-time quantitative polymerase chain reaction (PCR) and reactive oxygen species (ROS) generation. Cytotoxicity and apoptosis were measured by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and real-time quantitative PCR and flow cytometry, respectively. Finally, the involvement of mitogen-activated protein kinases (MAPK) was studied using Western blot. Results We found that AgNPs penetrated the cell membrane and localized inside the mitochondria. Co-incubation experiments resulted in increased oxidative stress, inflammation, and apoptosis. In addition, we found that co-exposure to both xenobiotics phosphorylated MAPK, particularly p42/44 MAPK. Conclusion A combined exposure of human fibroblasts to AgNPs and F results in increased cellular damage. Further studies are needed in order to evaluate pharmacological and potentially toxicological effects of AgNPs and F on oral health.

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confidence: 67%

Pharmacological and toxicological effects of co-exposure of human gingival fibroblasts to silver nanoparticles and sodium fluoride

Inkielewicz‐Stępniak¹,

Santos-Martínez²,

Medina³

et al. 2014

IJN

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“…* p<0.05; *** p<0.01. (17,21). In addition, other authors showed that fluoride does not induce DNA damage (22).…”

Section: Discussionmentioning

confidence: 97%

Fluoride modulates preosteoblasts viability and matrix metalloproteinases-2 and -9 activities

et al. 2012

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This study evaluated the influence of fluoride on cell viability and activity of matrix metalloproteinases (MMP) -2 and -9 secreted by preosteoblasts. Preosteoblasts (MC3T3-E1 murine cell line) were cultured in MEM medium supplement with 10% Fetal Bovine Serum (FBS) and nucleosides/ribonucleosides without ascorbic acid. Adherent cells were treated with different concentrations of F (as sodium fluoride-NaF) in medium (5 x 10 -6 M, 10 -5 M, 10 -4 M and 10 -3 M) for 24, 48, 72 and 96 h at 37 o C, 5% CO 2 . Control cells were cultivated in MEM only. After each period, preosteoblast viability was assessed by MTT assay. MMP-2 and -9 activities were performed by gel zymography. Also, alkaline phosphatase (ALP) activity was quantified by colorimetry in all experimental groups. It was shown that cultured cells with the highest dose of F (10 -3 M) for 96 h decreased preosteoblast viability while lower doses of F did not alter it, when compared to untreated cells. No differences were observed in ALP activity among groups. Moreover, compared to control, the treatment of cells with F at low dose slightly increased MMP-2 and -9 activities after 24 h. It was concluded that F modulates preosteoblast viability in a dose-dependent manner and also may regulate extracellular matrix remodeling.

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“…Thus, an exposure of the human promyelocytic HL-60 cells to 2-5 mM NaF led to significant increase in the level of cytosolic cytochrome c, activation of caspase-3, and subsequent cleavage of intact PARP leading to DNA damage [45,46,129]. In the same cells, Otsuki et al [47] reported an increased activity of caspase-9.…”

Section: Caspasesmentioning

confidence: 98%

Molecular Mechanisms of Cytotoxicity and Apoptosis Induced by Inorganic Fluoride

2012

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Fluoride (F) is ubiquitous natural substance and widespread industrial pollutant. Although low fluoride concentrations are beneficial for normal tooth and bone development, acute or chronic exposure to high fluoride doses results in adverse health effects. The molecular mechanisms underlying fluoride toxicity are different by nature. Fluoride is able to stimulate G-proteins with subsequent activation of downstream signal transduction pathways such as PKA-, PKC-, PI3-kinase-, Ca 2+ -, and MAPK-dependent systems. G-protein-independent routes include tyrosine phosphorylation and protein phosphatase inhibition. Along with other toxic effects, fluoride was shown to induce oxidative stress leading to excessive generation of ROS, lipid peroxidation, decrease in the GSH/GSSH ratio, and alterations in activities of antioxidant enzymes, as well as to inhibit glycolysis thus causing the depletion of cellular ATP and disturbances in cellular metabolism. Fluoride triggers the disruption of mitochondria outer membrane and release of cytochrome c into cytosol, what activates caspases-9 and -3 (intrinsic) apoptotic pathway. Extrinsic (death receptor) Fas/FasL-caspase-8 and -3 pathway was also described to be implicated in fluoride-induced apoptosis. Fluoride decreases the ratio of antiapoptotic/proapoptotic Bcl-2 family proteins and upregulates the expression of p53 protein. Finally, fluoride changes the expression profile of apoptosis-related genes and causes endoplasmic reticulum stress leading to inhibition of protein synthesis.

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Fluoride induces apoptosis by caspase-3 activation in human leukemia HL-60 cells

Cited by 64 publications

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Pharmacological and toxicological effects of co-exposure of human gingival fibroblasts to silver nanoparticles and sodium fluoride

Pharmacological and toxicological effects of co-exposure of human gingival fibroblasts to silver nanoparticles and sodium fluoride

Fluoride modulates preosteoblasts viability and matrix metalloproteinases-2 and -9 activities

Molecular Mechanisms of Cytotoxicity and Apoptosis Induced by Inorganic Fluoride

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