TXNDC12 inhibits lipid peroxidation and ferroptosis

Tang, Lanlan; Yu, Yan; Deng, Wenjun; Liu, Jiao; Wang, Yichun; Ye, Fanghua; Kang, Rui; Tang, Daolin; He, Qingnan

doi:10.1016/j.isci.2023.108393

Cited by 12 publications

(5 citation statements)

References 88 publications

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“…TXNDC proteins can exert antioxidant functions, and their elevated expression is associated with poor prognosis in many cancers [85,86]. A recent report implicated TXNDC12 in inhibiting lipid peroxidation and ferroptosis [87]. Even though SOCS1 has previously been shown to promote ferroptosis [88], it is possible that TXNDC12 was upregulated in Hepa-SOCS1 as a compensatory mechanism to maintain redox balance but contributed to the reduced lipid peroxidation in Hepa-SOCS1 cells following cisplatin or t-BHP, despite showing increased oxidative stress.…”

Section: Discussionmentioning

confidence: 99%

The Tumor Suppressor SOCS1 Diminishes Tolerance to Oxidative Stress in Hepatocellular Carcinoma

Shukla,

Khan,

Cayarga

et al. 2024

Cancers

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SOCS1 is a tumor suppressor in hepatocellular carcinoma (HCC). Recently, we showed that a loss of SOCS1 in hepatocytes promotes NRF2 activation. Here, we investigated how SOCS1 expression in HCC cells affected oxidative stress response and modulated the cellular proteome. Murine Hepa1-6 cells expressing SOCS1 (Hepa-SOCS1) or control vector (Hepa-Vector) were treated with cisplatin or tert-butyl hydroperoxide (t-BHP). The induction of NRF2 and its target genes, oxidative stress, lipid peroxidation, cell survival and cellular proteome profiles were evaluated. NRF2 induction was significantly reduced in Hepa-SOCS1 cells. The gene and protein expression of NRF2 targets were differentially induced in Hepa-Vector cells but markedly suppressed in Hepa-SOCS1 cells. Hepa-SOCS1 cells displayed an increased induction of reactive oxygen species but reduced lipid peroxidation. Nonetheless, Hepa-SOCS1 cells treated with cisplatin or t-BHP showed reduced survival. GCLC, poorly induced in Hepa-SOCS1 cells, showed a strong positive correlation with NFE2L2 and an inverse correlation with SOCS1 in the TCGA-LIHC transcriptomic data. A proteomic analysis of Hepa-Vector and Hepa-SOCS1 cells revealed that SOCS1 differentially modulated many proteins involved in diverse molecular pathways, including mitochondrial ROS generation and ROS detoxification, through peroxiredoxin and thioredoxin systems. Our findings indicate that maintaining sensitivity to oxidative stress is an important tumor suppression mechanism of SOCS1 in HCC.

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Section: Discussionmentioning

confidence: 99%

The Tumor Suppressor SOCS1 Diminishes Tolerance to Oxidative Stress in Hepatocellular Carcinoma

Shukla,

Khan,

Cayarga

et al. 2024

Cancers

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“…[48][49][50][51] In this context, ferroptosis, a form of irondependent non-apoptotic cell death, 52 emerges as a novel and promising approach for cancer therapy. [53][54][55][56][57][58][59] Despite its potential, the development of resistance to ferroptosis in cancer cells, along with its induction of immune cell death, constrains its application. 60,61 Consequently, there is a clinical need to foster more targeted and efficient forms of regulated cell death to combat cancer effectively.…”

Section: Discussionmentioning

confidence: 99%

Alkaliptosis induction counteracts paclitaxel‐resistant ovarian cancer cells via ATP6V0D1‐mediated ABCB1 inhibition

Chen,

Lin,

Kang

et al. 2024

Molecular Carcinogenesis

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Paclitaxel serves as the cornerstone chemotherapy for ovarian cancer, yet its prolonged administration frequently culminates in drug resistance, presenting a substantial challenge. Here we reported that inducing alkaliptosis, rather than apoptosis or ferroptosis, effectively overcomes paclitaxel resistance. Mechanistically, ATPase H+ transporting V0 subunit D1 (ATP6V0D1), a key regulator of alkaliptosis, plays a pivotal role by mediating the downregulation of ATP‐binding cassette subfamily B member 1 (ABCB1), a multidrug resistance protein. Both ATP6V0D1 overexpression through gene transfection and pharmacological enhancement of ATP6V0D1 protein stability using JTC801 effectively inhibit ABCB1 upregulation, resulting in growth inhibition in drug‐resistant cells. Additionally, increasing intracellular pH to alkaline (pH 8.5) via sodium hydroxide application suppresses ABCB1 expression, whereas reducing the pH to acidic conditions (pH 6.5) with hydrochloric acid amplifies ABCB1 expression in drug‐resistant cells. Collectively, these results indicate a potentially effective therapeutic strategy for targeting paclitaxel‐resistant ovarian cancer by inducing ATP6V0D1‐dependent alkaliptosis.

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“…The lipid peroxidation MDA assay kit (Beyotime, S0131) was employed to assess ferroptosis indicators following the manufacturer's instructions. Additionally, the lipid ROS level was analyzed using C11-BODIPY via flow cytometry [ [38] , [39] , [40] ].…”

Section: Methodsmentioning

confidence: 99%

Ciprofloxacin is a novel anti-ferroptotic antibiotic

Chen,

Tang,

Lin

et al. 2024

Heliyon

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TXNDC12 inhibits lipid peroxidation and ferroptosis

Cited by 12 publications

References 88 publications

The Tumor Suppressor SOCS1 Diminishes Tolerance to Oxidative Stress in Hepatocellular Carcinoma

The Tumor Suppressor SOCS1 Diminishes Tolerance to Oxidative Stress in Hepatocellular Carcinoma

Alkaliptosis induction counteracts paclitaxel‐resistant ovarian cancer cells via ATP6V0D1‐mediated ABCB1 inhibition

Ciprofloxacin is a novel anti-ferroptotic antibiotic

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