Arsenic trioxide increases apoptosis of SK-N-BE (2) cells partially by inducing GPX4-mediated ferroptosis

Feng, Chuchu; Wu, Yuechao; Chen, Yantao; Xiong, Xi; Peng, Xiaomin; Li, Chunmou; Weng, Wen-Jun; Zhu, Yong; Zhou, Dun-Hua; Li, Yang

doi:10.1007/s11033-022-07497-9

Cited by 15 publications

(7 citation statements)

References 47 publications

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“…According to the results of mRNA expression and protein expression, glycine significantly reduced the expression of TFR1 protein in jejunum and ileum after diquat stimulation, and significantly increased the expression of GPX4 protein in jejunum. Consistent with the results of many studies, it was found that the expression of the GPX4 gene could inhibit iron death and alleviate cell damage [ 43 , 44 , 45 ]. Xu et al have shown that dietary glycine can effectively inhibit the expression of TFR1, a key gene of ferroptosis, and promote the expression of GPX4, thereby alleviating liver injury induced by diquat [ 38 ].…”

Section: Discussionsupporting

confidence: 84%

Glycine Alleviated Intestinal Injury by Inhibiting Ferroptosis in Piglets Challenged with Diquat

Hua

et al. 2022

Animals

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The purpose of this research was to examine the impact of glycine on intestinal injury caused by oxidative stress in piglets. A 2 × 2 factorial experiment with diets (basic diet vs. 1% glycine diet) and oxidative stress (saline vs. diquat) was conducted on 32 weanling piglets. On day 21, all piglets received an injection of either saline or diquat. After 7 days, all pigs were slaughtered and intestinal samples were collected. Dietary glycine supplementation improved intestinal mucosal morphology, increased the activities of disaccharidases and enhanced intestinal mucosal antioxidant capacity, while regulating the expression of ferroptosis mediators in the piglets under oxidative stress. These findings suggested that dietary glycine supplementation improved the morphology and function of the intestinal mucosa, which was involved in regulating antioxidant capacity and ferroptosis.

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Section: Discussionsupporting

confidence: 84%

Glycine Alleviated Intestinal Injury by Inhibiting Ferroptosis in Piglets Challenged with Diquat

Hua

et al. 2022

Animals

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“…GPX4, a widely recognized antioxidant enzyme within the GPX system, plays a crucial role in impeding ferroptosis, which maintains the homeostasis of the cellular lipid bilayerby reducing toxic ROOH to non‐toxic ROH by using reduced GSH as a hydrogen donor 14 . Our previous study confirmed that the intracellular level of GPX4 protein significantly decreased after ATO treatment in NB cell lines, as revealed by off‐label quantitative proteomics techniques, however, the specific mechanism is still unclear 30 . As shown in Figure 4a,b, quantitative RT‐PCR (qRT‐PCR) results showed that ATO significantly inhibited GPX4 transcription in NB cells.…”

Section: Resultssupporting

confidence: 55%

“…14 Our previous study confirmed that the intracellular level of GPX4 protein significantly decreased after ATO treatment in NB cell lines, as revealed by off-label quantitative proteomics techniques, however, the specific mechanism is still unclear. 30 As shown in Figure 4a,b, quantitative RT-PCR (qRT-PCR) results showed that ATO significantly inhibited GPX4 transcription in NB cells. To detect whether ATO promotes the degradation of GPX4, we investigated the effect of ATO on GPX4 based on NB cells pretreated by a proteasome inhibitor MG132.…”

Section: Ato-mediated Ferroptosis Is Dependent On Gpx4 Transcriptiona...mentioning

confidence: 90%

“…Additionally, a previous study by our research team uncovered a substantial enrichment of differential proteins within the ferroptosis pathway subsequent to the administration of ATO to NB cell lines, as evidenced by off‐label quantitative proteomics methodologies. Notably, the expression of GPX4, a crucial rate‐limiting enzyme closely associated with the ferroptosis pathway, was markedly reduced 30 . However, the specific underlying mechanism remains elusive.…”

Section: Introductionmentioning

confidence: 99%

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Arsenic trioxide induces ferroptosis in neuroblastoma by mediating GPX4 transcriptional inhibition

Su,

Liu,

et al. 2024

Clinical Translational Sci

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Neuroblastoma (NB), the most common extracranial solid tumor in childhood, significantly contributes to cancer‐related mortality, presenting a dearth of efficacious treatment strategies. Previously, our studies have substantiated the potent cytotoxicity of arsenic trioxide (ATO) against NB cells, however, the specific underlying mechanism remains elusive. Here, we first identified ATO as a novel GPX4 inhibitor, which could trigger the ferroptosis in NB cells. In vitro, ATO significantly inhibited the proliferation and migration ability of NB cells SK‐N‐AS and SH‐SY5Y, and induced ferroptosis. Furthermore, the iron chelator deferoxamine reversed ATO‐mediated intracellular reactive oxygen species accumulation and hindered the generation of the lipid peroxidation product malondialdehyde. Conversely, ferric ammonium citrate notably intensified its cytotoxic effects, especially on retinoic acid (RA)‐resistant SK‐N‐AS cells. Subsequently, the quantitative real‐time polymerase chain reaction results showed ATO significantly inhibited the transcription of GPX4 in NB cells. Remarkably, immunoblotting analysis revealed that MG132 exhibited a notable effect on elevating GPX4 levels in NB cells. Nevertheless, pretreatment with MG132 failed to reverse the ATO‐mediated decrease in GPX4 levels. These findings suggested that ATO reduced the GPX4 expression level in NB cells by mediating GPX4 transcriptional repression rather than facilitating ubiquitinated degradation. In conclusion, our research has successfully indicated that ATO could induce ferroptosis and initiate lipid peroxidation by regulating the transcriptional repression of GPX4, and ATO holds promise as a potential anti‐tumor agent in NB, specifically for patients with RA‐resistant HR‐NB.

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“…Arsenic trioxide has attracted a lot of attention in recent months due to its ferroptosis-inducing properties in various cancer cells. It was shown to suppress proliferation of neuroblastoma cells by inhibiting the GSH-GPX4 pathway and activating numerous proteins known to play a role in ferritinophagy and iron overload [ 150 , 151 ]. It also caused rat cardiomyocyte H9c2 cell death, which involved the promotion of oxidative stress and was preventable by ferroptosis inhibitor Fer-1.…”

Section: Poisons and Toxicantsmentioning

confidence: 99%

Bioinorganic Modulators of Ferroptosis: A Review of Recent Findings

Bartos

Sikora

2023

IJMS

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Ferroptosis was first reported as a separate modality of regulated cell death in 2008 and distinguished under its current name in 2012 after it was first induced with erastin. In the following decade, multiple other chemical agents were researched for their pro- or anti-ferroptotic properties. Complex organic structures with numerous aromatic moieties make up the majority of this list. This review fills a more overlooked niche by gathering, outlining and setting out conclusions regarding less prominent cases of ferroptosis induced by bioinorganic compounds and reported on within the last few years. The article contains a short summary of the application of bioinorganic chemicals based on gallium, several chalcogens, transition metals and elements known as human toxicants used for the purpose of evoking ferroptotic cell death in vitro or in vivo. These are used in the form of free ions, salts, chelates, gaseous and solid oxides or nanoparticles. Knowledge of how exactly these modulators promote or inhibit ferroptosis could be beneficial in the context of future therapies aimed against cancer or neurodegenerative diseases, respectively.

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Arsenic trioxide increases apoptosis of SK-N-BE (2) cells partially by inducing GPX4-mediated ferroptosis

Cited by 15 publications

References 47 publications

Glycine Alleviated Intestinal Injury by Inhibiting Ferroptosis in Piglets Challenged with Diquat

Glycine Alleviated Intestinal Injury by Inhibiting Ferroptosis in Piglets Challenged with Diquat

Arsenic trioxide induces ferroptosis in neuroblastoma by mediating GPX4 transcriptional inhibition

Bioinorganic Modulators of Ferroptosis: A Review of Recent Findings

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