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Nrf2 depletion sensitizes pancreatic cancer cells to gemcitabine via aldehyde dehydrogenase 3a1 repression.

ABSTRACT: Nrf2 depletion sensitizes pancreatic cancer cells to gemcitabine via aldehyde dehydrogenase 3a1 repression.

PROVIDER: PRJNA721874 | ENA |

REPOSITORIES: ENA

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Nrf2 depletion sensitizes pancreatic cancer cells to gemcitabine via aldehyde dehydrogenase 3a1 repression.

Project description:The central regulator of oxidative stress responses, Nrf2, is attracting great interest as a therapeutic target in various cancers. Explorations of novel Nrf2 inhibitors have been reported, which suggest future clinical applications. Halofuginone, the derivative of natural plant alkaloid, has been reported to deplete Nrf2 rapidly in cancer cells with Nrf2 activation. In the current study, we identified that halofuginone sensitizes pancreatic cancer cells to gemcitabine, both in vitro and in vivo settings. We identified downregulation of Aldh3a1 in mouse pancreatic cancer cell lines after halofuginone treatment. The Nrf2 inducer diethyl maleate treatment upregulated Aldh3a1, and Nrf2 deleted pancreatic cancer cell lines failed to show induction. Knockdown of Aldh3a1 also sensitized cancer cells to gemcitabine, suggesting contribution of Aldh3a1 to gemcitabine resistance as a downstream target of Nrf2. Current study confirmed the therapeutic benefits of halofuginone in pancreatic cancer.

2021-12-21 | GSE172046 | GEO

Empagliflozin Ameliorates Aldehyde Dehydrogenase 2 Deficiency-induced Endothelial Dysfunction

Project description:Empagliflozin Ameliorates Aldehyde Dehydrogenase 2 Deficiency-induced Endothelial Dysfunction

| PRJNA764589 | ENA

Gene expression data from endometrial cancer patient-derived cells (PDCs) treated with aldehyde dehydrogenase inhibitor

Project description:Three lines of PDCs (EnC-A, EnC-B, and EnC-C) were established from endometrial cancer specimens. Aldehyde dehydrogenase (ALDH) inhibition repressed the cell growth with altered gene expression.

2022-02-22 | GSE127239 | GEO

Analysis of tumor cell plasticity in endometrioid carcinoma using cancer stem cell marker aldehyde dehydrogenase (ALDH)

Project description:To investigate the tumor cell plasticity using aldehyde dehydrogenase (ALDH) 1A1 activity, we established two distinct HEC-1B sublines, in which ALDH1A1-high population accelerated such transition and ALDH1A1-high population did not show such acceleration.

2022-11-30 | GSE212889 | GEO

Role of aldehyde dehydrogenase on the metabolic regulation in Clostridium ljungdahlii fermentation

Project description:Clostridium ljungdahlii not only utilizes CO, but also H2 as energy source during autotrophic growth. And C. ljungdahlii also grows in fructose fermentation. In theory, fructose is a more energetically favourable energy source than syngas in the fermentation of C. ljungdahlii. However, C. ljungdahlii grows insufficiently in fructose and produces less acetate and ethanol, compared to syngas fermentation. In this study, C. ljungdahlii wild type and mutants were fermented on fructose. C. ljungdahlii produced less ethanol than the ΔadhE1 mutant and consumed less fructose. The ΔadhE1+2 mutant cannot grow in the syngas fermentation and produced less ethanol among the three strains. The results showed that aldehyde dehydrogenase inactivation led to efficient metabolism in C. ljungdahlii and the bifunctional aldehyde/alcohol dehydrogenases inactivation led to decrease metabolism. Thus, comparative transcriptomes among cells grown on fructose of three strains were performed to investigate gene expression profiles based on three biological replicates.

2023-06-27 | E-MTAB-13020 | biostudies-arrayexpress

Nuclear receptor NHR-49 promotes peroxisome proliferation to compensate for aldehyde dehydrogenase deficiency in C. elegans

Project description:The intracellular level of fatty aldehydes is tightly regulated to minimize the formation of toxic aldehyde adducts of cellular components. Accordingly, deficiency of a fatty aldehyde dehydrogenase FALDH causes the neurologic disorder Sjögren-Larsson syndrome (SLS) in humans. However, cellular responses to unresolved, elevated fatty aldehyde levels are poorly understood. Based on lipidomic and imaging analysis, we report that the loss of endoplasmic reticulum-, mitochondria- and peroxisomes-associated ALH-4, the C. elegans FALDH ortholog, increases fatty aldehyde levels and reduces fat storage. ALH-4 deficiency in the intestine, cell-nonautonomously induces NHR-49/NHR-79-dependent hypodermal peroxisome proliferation. This is accompanied by the upregulation of catalases and fatty acid catabolic enzymes, as indicated by RNA sequencing. Such a response is required to counteract ALH-4 deficiency since alh-4; nhr-49 double mutant animals are not viable. Our work reveals unexpected inter-tissue communication of fatty aldehyde levels, and suggests pharmacological modulation of peroxisome proliferation as a therapeutic strategy for SLS.

2021-06-07 | GSE162792 | GEO

2 Role of aldehyde dehydrogenase on the metabolic regulation in Clostridium ljungdahlii fermentation

Project description:Clostridium ljungdahlii can utilize CO as energy source during autotrophic growth. C. ljungdahlii grows sufficiently in CO and produces ethanol as the main product. In this study, C. ljungdahlii wild type and mutant were fermented on CO. C. ljungdahlii produced more ethanol than the ΔadhE1 mutant. The results showed that aldehyde dehydrogenase inactivation led to inefficient metabolism in C. ljungdahlii. Thus, comparative transcriptomes among cells grown on CO of WT and ΔadhE1 mutant were performed to investigate gene expression profiles based on three biological replicates.

2023-06-27 | E-MTAB-13021 | biostudies-arrayexpress

Metabolic effects of novel aldehyde dehydrogenase inhibitors (ALDH) inhibitors

Project description:Effect of novel aldehyde dehydrogenase inhibitors. Before an experiment medium was replaced to medium without glucose with addition of labeled glucose on C13. Next, cells were treated with ALDH inhibitors 673 or 773 for 1, 4, or 8 hr (673&773-Jan26)

2017-06-19 | ST000774 | MetabolomicsWorkbench

Role of aldehyde dehydrogenase on the metabolic regulation in Clostridium ljungdahlii fermentation

Project description:Role of aldehyde dehydrogenase on the metabolic regulation in Clostridium ljungdahlii fermentation

| PRJEB62861 | ENA

Impact of Aldehyde Dehydrogenase Inhibition on the Stemness of Endometrial Cancer Stem Cells

Project description:Cancer stem cells (CSCs) are crucial for tumor initiation, growth, dissemination, and resistance to therapy. In this study, we aimed to evaluate the effect of inhibiting aldehyde dehydrogenase (ALDH), an enzyme present in endometrial CSCs, using N,N-diethylaminobenzaldehyde (DEAB). This study aimed to evaluate the effects of ALDH inhibition in endometrial cancer stem cells (CSCs). ECC-1 and RL95-2 cell lines were subjected to proteome profiling with and without N,N-diethylaminobenzaldehyde (DEAB).

2024-06-23 | PXD052364 | Pride

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