Antimony-trioxide- and arsenic-trioxide-induced apoptosis in myelogenic and lymphatic cell lines, recruitment of caspases, and loss of mitochondrial membrane potential are enhanced by modulators of the cellular glutathione redox system

Lösler, Susan; Schlief, Sarah; Kneifel, Christiane; Thiel, Eckhard; Schrezenmeier, Hubert; Rojewski, Markus

doi:10.1007/s00277-009-0736-4

Cited by 21 publications

(11 citation statements)

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“…Several in vitro studies have described the induction of apoptosis by trivalent antimony through activation of caspase-3 (Lecureur et al 2002a, b; Losler et al 2009; Mann et al 2006; Muller et al 1998; Wyllie and Fairlamb 2006). Lecureur et al (2002b) pointed out that the cytotoxic potassium antimonyl tartrate concentrations action on human lymphoma Daudi cells and on B lymphocytes from leukemia patients were in micromolar concentrations; concentrations that are likely to be achievable in vivo in humans (Schulert et al 1966).…”

Section: Discussionmentioning

confidence: 99%

“…Antimony, which belongs to the same group (Group V) of the periodic table as arsenic, shares numerous biological features with this metalloid (Gebel 1997). Arsenic trioxide induces oxidative damage, activates caspase-3, and induces apoptosis in human leucocyte cells, and the toxic cellular effects are greater than that induced by a corresponding dose of antimonial compounds (Losler et al 2009). In the NHANES 1999–2000 and 2001–2002 cycles, arsenic was not measured, thus we may not know whether the observed associations might be due to arsenic co-exposure.…”

Section: Discussionmentioning

confidence: 99%

“…It also rapidly accumulates in blood cells following in vivo administration (Winship 1987). Several in vitro studies report that antimony generates reactive oxygen species (ROS) and activates caspase-3 leading to cell apoptosis in human leukocyte cell lines (Lecureur et al 2000a, b; Losler et al 2009; Wyllie and Fairlamb 2006). …”

Section: Introductionmentioning

confidence: 99%

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Urinary antimony and leukocyte telomere length: An analysis of NHANES 1999–2002

Scinicariello

Buser

2016

Environmental Research

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Telomeres are repetitive DNA sequences (TTAGGG) at the end of chromosomes. Cells with critically short telomeres enter replicative senescence and apoptosis. Several in vitro studies report that antimony causes cell apoptosis in human leukocyte cell lines. The goal of this analysis was to investigate whether there is an association between antimony exposure and leukocyte telomere length (LTL) among US adults aged 20 and older based on the National Health and Nutrition Examination Survey (NHANES) 1999–2002. We used multivariate linear regression to analyze the association of urinary antimony with LTL. LTL was log-natural transformed and the results were re-transformed and presented as percent differences. After adjustment for potential confounders, individuals in the 3rd and 4th quartiles of urinary antimony had statistically significantly shorter LTL (−4.78%, 95% CI: −8.42, −0.90; and −6.11%, 95% CI: −11.04, −1.00, respectively) compared to the lowest referent quartile, with evidence of a dose-response relationship (p-value for trend = 0.03). Shorter LTL with antimony was driven by middle aged (40–59 years) and older (60–85 years) adult groups. The association may be biologically plausible because of reported oxidative stress and apoptosis effects of antimony on blood cells, effects known to shorten telomere length.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Urinary antimony and leukocyte telomere length: An analysis of NHANES 1999–2002

Scinicariello

Buser

2016

Environmental Research

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“…The generation of reactive oxygen species has also been postulated to play a role in antimony toxicity [37]. Antimony-associated apoptosis is attributed to depletion of glutathione capacity and subsequent enhancement of reactive oxygen species formation [38,39].…”

Section: Pathophysiology Of Toxic Effectsmentioning

confidence: 99%

Antimony and Nickel

Sztajnkrycer¹

2016

Critical Care Toxicology

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“…Recent reports suggest that BSO sensitizes antihormone- resistant breast cancer cells to estradiol treatment [7], [8]. Antimony-trioxide- and arsenic-trioxide-induced apoptosis in myelogenic and lymphatic cell lines is enhanced by BSO [9]. Enhanced anti-leukemic activity is also seen in combination treatment of BSO and Kanamycin F [10].…”

Section: Introductionmentioning

confidence: 99%

Synergistic Apoptosis of CML Cells by Buthionine Sulfoximine and Hydroxychavicol Correlates with Activation of AIF and GSH-ROS-JNK-ERK-iNOS Pathway

et al. 2013

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BackgroundHydroxychavicol (HCH), a constituent of Piper betle leaf has been reported to exert anti-leukemic activity through induction of reactive oxygen species (ROS). The aim of the study is to optimize the oxidative stress –induced chronic myeloid leukemic (CML) cell death by combining glutathione synthesis inhibitor, buthionine sulfoximine (BSO) with HCH and studying the underlying mechanism.Materials and MethodsAnti-proliferative activity of BSO and HCH alone or in combination against a number of leukemic (K562, KCL22, KU812, U937, Molt4), non-leukemic (A549, MIA-PaCa2, PC-3, HepG2) cancer cell lines and normal cell lines (NIH3T3, Vero) was measured by MTT assay. Apoptotic activity in CML cell line K562 was detected by flow cytometry (FCM) after staining with annexinV-FITC/propidium iodide (PI), detection of reduced mitochondrial membrane potential after staining with JC-1, cleavage of caspase- 3 and poly (ADP)-ribose polymerase proteins by western blot analysis and translocation of apoptosis inducing factor (AIF) by confocal microscopy. Intracellular reduced glutathione (GSH) was measured by colorimetric assay using GSH assay kit. 2′,7′-dichlorodihydrofluorescein diacetate (DCF-DA) and 4-amino-5-methylamino-2′,7′-difluorofluorescein (DAF-FM) were used as probes to measure intracellular increase in ROS and nitric oxide (NO) levels respectively. Multiple techniques like siRNA transfection and pharmacological inhibition were used to understand the mechanisms of action.ResultsNon-apoptotic concentrations of BSO significantly potentiated HCH-induced apoptosis in K562 cells. BSO potentiated apoptosis-inducing activity of HCH in CML cells by caspase-dependent as well as caspase-independent but apoptosis inducing factor (AIF)-dependent manner. Enhanced depletion of intracellular GSH induced by combined treatment correlated with induction of ROS. Activation of ROS- dependent JNK played a crucial role in ERK1/2 activation which subsequently induced the expression of inducible nitric oxide synthase (iNOS). iNOS- mediated production of NO was identified as an effector molecule causing apoptosis of CML cells.Conclusion/SignificanceBSO synergizes with HCH in inducing apoptosis of CML cells through the GSH-ROS-JNK-ERK-iNOS pathway.

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Antimony-trioxide- and arsenic-trioxide-induced apoptosis in myelogenic and lymphatic cell lines, recruitment of caspases, and loss of mitochondrial membrane potential are enhanced by modulators of the cellular glutathione redox system

Cited by 21 publications

References 52 publications

Urinary antimony and leukocyte telomere length: An analysis of NHANES 1999–2002

Urinary antimony and leukocyte telomere length: An analysis of NHANES 1999–2002

Antimony and Nickel

Synergistic Apoptosis of CML Cells by Buthionine Sulfoximine and Hydroxychavicol Correlates with Activation of AIF and GSH-ROS-JNK-ERK-iNOS Pathway

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