Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Effect of mitochondria-targeted derivative of curcumin (Mitocurcumin; MC ) on gene expression in human Triple Negative Breast Cancer cell line, MDA-MB-231.

ABSTRACT: RNA sequencing was performed to elucidate the anti-cancer mechanism of action of mitocurcumin in MDA-MB-231 Triple Negative Breast Cancer cells. Transcriptomic analysis revealed that mitocurcumin-treatment led to significant down-regulation of genes regulating cell proliferation, differentiation, vasculature development and DNA-binding transcription activator activity while the significantly up-regulated genes associated with starvation, oxidative stress, response to unfolded proteins and topologically incorrect proteins and intrinsic apoptosis. Mechanistically, in vitro and transcriptomics confirmed mitocurcumin-mediated induction of mitochondrial oxidative stress, bioenergetic stress and proteotoxic stress culminating in apoptosis.

ORGANISM(S): Homo sapiens

PROVIDER: GSE276992 | GEO | 2025/09/10

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Mutant CHCHD10 causes an extensive metabolic rewiring that precedes OXPHOS dysfunction in a murine model of mitochondrial cardiomyopathy

Project description:Mitochondrial cardiomyopathies are fatal diseases, with no effective treatment. Alterations of heart mitochondrial function activate the mitochondrial integrated stress response (ISRmt), a transcriptional program affecting cell metabolism, mitochondrial biogenesis, and proteostasis. In humans, mutations in CHCHD10, a mitochondrial protein with unknown function, were recently associated with dominant multi-system mitochondrial diseases, whose pathogenic mechanisms remain to be elucidated. Here, in CHCHD10 knock-in mutant mice, we identify an extensive cardiac metabolic rewiring triggered by proteotoxic ISRmt. The stress response arises early on, before the onset of bioenergetic impairments, triggering a switch from oxidative to glycolytic metabolism, enhancement of transsulfuration and one carbon (1C) metabolism, and widespread metabolic imbalance. In parallel, increased NADPH oxidases elicit antioxidant responses leading to heme depletion. As the disease progresses, the adaptive metabolic stress response fails, resulting in fatal cardiomyopathy. Our findings suggest that early interventions to counteract metabolic imbalance could ameliorate mitochondrial cardiomyopathy associated with proteotoxic ISRmt.

2022-03-01 | PXD031444 | Pride

WTAP and m6A-dependent circRNAs modulation during stress response in acute myeloid leukemia progenitor cells

Project description:N6-methyladenosine (m6A) is one of the most prevalent and conserved RNA modifications. It controls several biological processes, including the biogenesis and function of circular RNAs (circRNAs), which are a class of covalently closed-single stranded RNAs. Several studies have revealed that proteotoxic stress response induction could be a relevant anticancer therapy in Acute Myeloid Leukemia (AML). Furthermore, it has emerged a strong molecular interaction between the m6A mRNA modification factors and the suppression of the proteotoxic stress response. Since the proteasome inhibition leading to the imbalance in protein homeostasis is strictly linked to the stress response induction, we investigated the role of Bortezomib (Btz) on m6A regulation and in particular its impact on the modulation of m6A-dependent circRNAs expression. Here, we show that the treatment of AML cells with Btz downregulated the expression of the m6A regulator WTAP at translational level, mainly because of increased oxidative stress. Indeed, Btz treatment promoted oxidative stress, with ROS generation and HMOX-1 activation and administration of the reducing agent N-acetylcysteine restored WTAP expression. Additionally, we identified m6A-modified circRNAs modulated by Btz treatment, including circHIPK3, which is implicated in protein folding and oxidative stress regulation upon silencing. These results highlight the intricate molecular networks involved in oxidative and ER stress induction in AML cells following proteotoxic stress response, laying the groundwork for future therapeutic strategies targeting these pathways.

2024-06-06 | GSE262829 | GEO

Impact of curcumin on human monocytes (U937 cells) exposed to oxidative stress

Project description:Oxidative stress as a result of cigarette smoking is an important etiological factor in the pathogenesis of chronic obstructive pulmonary disease (COPD), a chronic steroid-insensitive inflammatory disease of the airways. The activity of the transcriptional co-repressor Histone deacetylase-2 (HDAC2) is dramatically reduced in COPD and cells exposed to oxidative stress or cigarette smoke. Moreover, curcumin (diferuloylmethane), a dietary polyphenol, at concentrations upto 1uM specifically restores cigarette smoke extract (CSE)- or oxidative stress- impaired HDAC2 activity. The aim of this study was to therefore identify any links through those gene sets that are affected by oxidative stress and subsequent treatment with curcumin in order to determine whether or not this could explain the impact of curcumin on restoration of oxidant impaired HDAC2 transcriptional co-repressor activity. Keywords: time course

2008-03-20 | GSE10896 | GEO

Loss of ATG7 in Microglia Impairs UPR, Triggers Ferroptosis and Weakens Amyloid Pathology Control [bulk RNA-seq]

Project description:Microglia impact brain development, homeostasis, and pathology. One important microglial function in Alzheimer’s Disease (AD) is to contain proteotoxic amyloid β (Aβ) plaques. Recent studies reported the involvement of autophagy-related (ATG) proteins in this process. Here we found that microglia-specific deletion of Atg7 in an AD mouse model impaired microglia coverage of Aβ plaques, increasing plaque diffusion and neurotoxicity. Single-cell RNA sequencing, biochemical and immunofluorescence analyses revealed that Atg7 deficiency reduces unfolded protein response (UPR) while increasing oxidative stress. Cellular assays demonstrated that these changes lead to lipoperoxidation and ferroptosis of microglia. In aged mice without Aβ build-up, UPR reduction and increase oxidative damage induced by Atg7 deletion did not impact microglia numbers. We conclude that reduced UPR and increased oxidative stress in Atg7-deficient microglia lead to ferroptosis when exposed to proteotoxic stress from Aβ plaques. However, these microglia can still manage misfolded protein accumulation as they age.

2025-01-30 | GSE286095 | GEO

Loss of ATG7 in Microglia Impairs UPR, Triggers Ferroptosis and Weakens Amyloid Pathology Control [scRNA-seq]

2025-01-30 | GSE286094 | GEO

Genomic analysis of xCT-mediated regulatory network: identification of novel targets against AIDS-associated lymphoma

Project description:Kaposi’s sarcoma-associated herpesvirus (KSHV) is the etiological agent of primary effusion lymphoma (PEL), a rapidly progressing malignancy mostly arising in HIV-infected patients. Even under conventional chemotherapy, PEL continues to portend nearly 100% mortality within several months, which urgently requires novel therapeutic strategies. We have previously demonstrated that targeting xCT, an amino acid transporter for cystine/glutamate exchange, induces significant PEL cell apoptosis through regulation of multiple host and viral factors. More importantly, one of xCT selective inhibitors, Sulfasalazine (SASP), effectively prevents PEL tumor progression in an immune-deficient xenograft model. In the current study, we use Illumina microarray to explore the genomic gene profile altered by SASP treatment within 3 KSHV+ PEL cell-lines, and discover that many genes involved in oxidative stress/antioxidant defense system, apoptosis/anti-apoptosis/cell death, and cellular response to unfolded proteins/topologically incorrect proteins are potentially regulated by xCT. We further functionally validate 2 downstream candidates, OSGIN1 (Oxidative stress-induced growth inhibitor 1) and XRCC5 (X-ray repair cross-complementing protein 5), their relationship with PEL cell survival/proliferation and chemoresistance, respectively. Together, our data indicate that targeting these xCT-regulated novel downstream genes may help devise promising therapeutic strategies against PEL and/or other AIDS-related lymphoma.

2015-11-23 | GSE65418 | GEO

Genomic analysis of xCT-mediated regulatory network: identification of novel targets against AIDS-associated lymphoma

Project description:Kaposiâs sarcoma-associated herpesvirus (KSHV) is the etiological agent of primary effusion lymphoma (PEL), a rapidly progressing malignancy mostly arising in HIV-infected patients. Even under conventional chemotherapy, PEL continues to portend nearly 100% mortality within several months, which urgently requires novel therapeutic strategies. We have previously demonstrated that targeting xCT, an amino acid transporter for cystine/glutamate exchange, induces significant PEL cell apoptosis through regulation of multiple host and viral factors. More importantly, one of xCT selective inhibitors, Sulfasalazine (SASP), effectively prevents PEL tumor progression in an immune-deficient xenograft model. In the current study, we use Illumina microarray to explore the genomic gene profile altered by SASP treatment within 3 KSHV+ PEL cell-lines, and discover that many genes involved in oxidative stress/antioxidant defense system, apoptosis/anti-apoptosis/cell death, and cellular response to unfolded proteins/topologically incorrect proteins are potentially regulated by xCT. We further functionally validate 2 downstream candidates, OSGIN1 (Oxidative stress-induced growth inhibitor 1) and XRCC5 (X-ray repair cross-complementing protein 5), their relationship with PEL cell survival/proliferation and chemoresistance, respectively. Together, our data indicate that targeting these xCT-regulated novel downstream genes may help devise promising therapeutic strategies against PEL and/or other AIDS-related lymphoma. 3 KSHV PEL cell lines were treated with xCT selective inhibitor Sulfasalazine (SASP) and the gene expression signature was compared to that of untreated cells

2015-11-23 | E-GEOD-65418 | biostudies-arrayexpress

Transcription profiling of human monocytes (U937 cell line) to assess the impact of curcumin on monocytes exposed to oxidative stress

Project description:Oxidative stress as a result of cigarette smoking is an important etiological factor in the pathogenesis of chronic obstructive pulmonary disease (COPD), a chronic steroid-insensitive inflammatory disease of the airways. The activity of the transcriptional co-repressor Histone deacetylase-2 (HDAC2) is dramatically reduced in COPD and cells exposed to oxidative stress or cigarette smoke. Moreover, curcumin (diferuloylmethane), a dietary polyphenol, at concentrations up to 1uM specifically restores cigarette smoke extract (CSE)- or oxidative stress- impaired HDAC2 activity. The aim of this study was to therefore identify any links through those gene sets that are affected by oxidative stress and subsequent treatment with curcumin in order to determine whether or not this could explain the impact of curcumin on restoration of oxidant impaired HDAC2 transcriptional co-repressor activity. Experiment Overall Design: Human PMA-differentiated U937 cells, unexposed or exposed to oxidative stress (100mM H2O2) were either left untreated or treated with curcumin (1 mM) for either 4 or 18 hr. Performed in triplicate

2009-12-17 | E-GEOD-10896 | biostudies-arrayexpress

Enhanced glutathione levels confer resistance to apoptotic and ferroptotic programmed cell death in NEIL DNA glycosylase deficient HAP1 cells

Project description:The NTHL1 and NEIL1-3 DNA glycosylases are major enzymes in the removal of oxidative DNA base lesions, via the base excision repair (BER) pathway. To investigate their interplay in human cells, we engineered single, double, triple, and quadruple DNA glycosylase deficient HAP1 cells using the Crisp-cas 9 technology. We found that these DNA glycosylase deficient cells are more resistant to oxidative stress caused by genotoxic agents than wild type cells, and a further augment in resistance was observed upon inhibition of glutathione synthesis. Gene expression analysis revealed that GSH depletion activates the NRF2/KEAP1 pathway and ER stress induced apoptosis. Furthermore, glutathione depleted NEIL triple KO cells are also more resistant to cell death induced via ferroptosis than wild type cells. Finally, we observed higher basal level of glutathione and differential expression of NRF2-regulated genes associated with glutathione homeostasis in these cells. We propose that NEIL deficiency leads to aberrant transcription and subsequent errors in protein synthesis, which cause ER- and proteotoxic stress. This triggers the unfolded protein response, which consequently upregulates intracellular antioxidant defence mechanisms. Altogether, our data suggest that NEIL deficient cells developed an oxidative stress defence mechanism termed hormesis mediated by elevated GSH levels in response to the increased intracellular stress inflicted by loss of NEIL123 activities.

2023-09-08 | GSE242290 | GEO

Proteotoxic stress-induced apoptosis in cancer cells: understanding the susceptibility and enhancing the potency

Project description:Proteotoxic stress-induced apoptosis in cancer cells: understanding the susceptibility and enhancing the potency

| PRJNA846688 | ENA