Sodium arsenite and arsenic trioxide differently affect the oxidative stress, genotoxicity and apoptosis in A549 cells: An implication for the paradoxical mechanism

Jiang, Xuejun; Chen, Chengzhi; Zhao, Wei; Zhang, Zunzhen

doi:10.1016/j.etap.2013.08.002

Cited by 59 publications

(35 citation statements)

References 56 publications

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“…Our analysis of the DNA damage through evaluation of γ-H2AX histone expression showed that NP realgar and ATO exhibit similar effects preferentially at higher concentration tested. In contrast, comparison of another pair of arsenic compounds -a therapeutic drug ATO, with a potent carcinogen sodium arsenite, revealed that ATO caused more severe damage in lung adenocarcinoma A549 cells than sodium arsenite [45]. The only difference, still quantitative, that we have found between action of ATO and NP realgar, is in the course of autophagy; with the autophagic flux dominating at lower concentrations and the switch to apoptosis occurring at higher concentrations of both forms of arsenic.…”

Section: Discussionmentioning

confidence: 39%

Section: Discussionmentioning

confidence: 80%

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Realgar (As4S4) nanoparticles and arsenic trioxide (As2O3) induced autophagy and apoptosis in human melanoma cells in vitro

Pastorek¹,

Gronesova²,

Cholujová³

et al. 2014

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The aim of the present study was to compare the effect of realgar nanoparticles and arsenic trioxide (ATO) on viability, DNA damage, proliferation, autophagy and apoptosis in the human melanoma cell lines BOWES and A375. The application of various flow cytometric methods for measurements cell viability, DNA cell cycle, mitochondrial potential, lysosomal activity, and intracellular content of glutathione was used. In addition, quantitative PCR, western blotting and multiplex bead array analyses were applied for evaluation of redox stress, autophagic flux, and cell signaling alterations.The results showed that realgar treatment of studied cells caused modulation of cell proliferation, induced a block in G2/M phase of the cell cycle and altered phosphorylation of IκB, Akt, ERK1/2, p38, and JNK kinases, as well as decreased mitochondrial membrane potential. Additionally, it appeared that induction of cell death by both realgar and ATO was dose-dependent, when lower (0.3 µM) dosage increased lysosomal activity and induced autophagy and higher (1.25 µM) concentration resulted in the appearance of apoptosis, while pan-caspase inhibitor attenuated more efficiently realgar-than ATO-induced cell death. Furthermore, low concentrations of ATO and realgar nanoparticles increased the content of intracellular glutathione and elevated γ-H2AX expression confirmed DNA damage preferentially at higher concentrations of both drugs used. Further analysis revealed slight differences in time-dependent phosphorylation pattern due to both realgar and ATO treatments, while significant differences were noticed between cell lines.In conclusion, realgar nanoparticles and ATO treatment induced dose-dependent activation of autophagy and apoptosis in both melanoma cell lines, when autophagy flux was determined at lower drug concentrations and the switch to apoptosis occurred at higher concentrations of both arsenic forms.Key words : realgar, autophagy, cell cycle, DNA damage, Nrf2, chloroquine, glutathione Arsenic has been accepted to be a poison for years and it is generally considered as an extremely effective environmental co-carcinogen for some human malignancies, especially for skin and lung cancer [1]. The toxicity of arsenicals depends on their chemical states, exposure dose, the biological species, age and gender, as well as on individual susceptibilities, genetic and nutritional factors [2]. Largely, to living organisms methylated trivalent arsenicals are more toxic and pentavalent metabolites are less toxic than arsenite (iAs III ) [3,4]. In 2002, a pilot clinical study of pure realgar in treatment of patients with APL was conducted in China, and impressive responses were achieved and reported [5]. Realgar is a mineral composed mainly of tetra-arsenic tetra-sulfide (As 4 S 4 ), which is also called red arsenic due to its a deep red color (Xionghuang in Chinese). Low solubility of arsenic in realgar, using water as a solvent (0.4%), can be increased to approximately 1.5% by leaching in artificial body fluid [6]. Higher proportion of...

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Section: Discussionmentioning

confidence: 39%

Section: Discussionmentioning

confidence: 80%

Realgar (As4S4) nanoparticles and arsenic trioxide (As2O3) induced autophagy and apoptosis in human melanoma cells in vitro

Pastorek¹,

Gronesova²,

Cholujová³

et al. 2014

neo

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“…It has been reported that intracellular ROS levels produced is dependent on the concentration of sodium arsenite which further determine the type and severity of biological/pathological effects [8]. However, sodium arsenite effect has been associated with hormetic properties in which low dose stimulation and high dose inhibition is expected.…”

Section: Introductionmentioning

confidence: 99%

Sodium arsenite-induced cardiovascular and renal dysfunction in rat via oxidative stress and protein kinase B (Akt/PKB) signaling pathway

et al. 2017

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(2017) Sodium arsenite-induced cardiovascular and renal dysfunction in rat via oxidative stress and protein kinase B (Akt/PKB) signaling pathway, Redox Report, 22:6, 467-477, DOI: 10.1080/13510002.2017 Objectives: Arsenic is a ubiquitous element that is widely distributed in the environment to which man and animals are exposed. Cardiovascular disease is one of the aftermaths of chronic arsenic exposure-related morbidity and mortality. This study sought to investigate the possibility of reversal from arsenic-induced cardio-renal toxicity following exposure and subsequent withdrawal. The study also seeks to understand the mechanism of action of this reversal. Methods: Rats were orally exposed to sodium arsenite at 10, 20 and 40 mg/kg daily for 4 weeks followed by 4 weeks of withdrawal. Results: Exposure to arsenic caused a significant increase in malondialdehyde, H 2 O 2 generation but decrease total thiol and reduced glutathione levels in both cardiac and renal tissues. Furthermore, increases in superoxide dismutase, glutathione-S-transferase and catalase with significant increases in glutathione peroxidase activities were observed in the cardiac tissues. On the contrary, a significant reduction in the renal antioxidant enzyme activity was recorded following exposure. Also, antioxidant defense system did not return to apparent values after arsenic withdrawal. Immunohistochemistry revealed a reduction in the expression of the prosurvival protein-protein kinase B (Akt/PKB) following exposure to arsenic and this was not reversed by withdrawal Discussion: Exposure to arsenic caused cardio-renal toxicity via induction of oxidative stress and down-regulation of Akt/PKB expressions.

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“…Moreover, its antitumor activity has been confirmed in non-APL leukemia (9) and solid tumor cell lines (16,25,39). As 2 O 3 induces apoptosis and inhibits the growth of various types of tumor cells in vitro, but relatively higher concentrations are required for solid tumor cells than for hematologic cancer cells (40,41).…”

Section: Discussionmentioning

confidence: 90%

Inactivation of Akt by arsenic trioxide induces cell death via mitochondrial-mediated apoptotic signaling in SGC-7901 human gastric cancer cells

et al. 2014

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Abstract. Arsenic trioxide (As 2 O 3 ) has been recognized as a potential chemotherapeutic agent, yet the details concerning its mechanism of action in solid cancers remain undetermined. The present study assessed the role of Akt in the cell death induced by As 2 O 3 . The MTT assay showed that As 2 O 3 suppressed the proliferation of SGC-7901 cells in a dose-and time-dependent manner. Characteristic apoptotic changes were observed in the As 2 O 3 -treated cells by Hoechst 33342 staining, and FACS analysis showed that As 2 O 3 caused dose-dependent apoptotic cell death. As 2 O 3 activated caspase-3 and -9, and PARP cleavage in a dose-dependent manner. Compromised mitochondrial membrane potential and an increased protein level of Bax indicated involvement of mitochondia. As 2 O 3 decreased the levels of p-Akt (Ser473), p-Akt (Thr308) and p-GSK-3β (Ser9), suggesting that As 2 O 3 inactivated Akt kinase. In addition, LY294002 (a PI3 kinase inhibitor) augmented the apoptosis induced by As 2 O 3 . These results demonstrated that inhibition of PI3K/Akt signaling was involved in As 2 O 3 -induced apoptosis of gastric cancer SGC-7901 cells.

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Sodium arsenite and arsenic trioxide differently affect the oxidative stress, genotoxicity and apoptosis in A549 cells: An implication for the paradoxical mechanism

Cited by 59 publications

References 56 publications

Realgar (As4S4) nanoparticles and arsenic trioxide (As2O3) induced autophagy and apoptosis in human melanoma cells in vitro

Realgar (As4S4) nanoparticles and arsenic trioxide (As2O3) induced autophagy and apoptosis in human melanoma cells in vitro

Sodium arsenite-induced cardiovascular and renal dysfunction in rat via oxidative stress and protein kinase B (Akt/PKB) signaling pathway

Inactivation of Akt by arsenic trioxide induces cell death via mitochondrial-mediated apoptotic signaling in SGC-7901 human gastric cancer cells

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