Change in gene expression of a canine melanoma cell line caused by exposure to nonsteroidal anti-inflammatory drugs (NSAIDs) .
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ABSTRACT:
ORGANISM(S): Canis lupus familiaris
PROVIDER: GSE78988 | GEO | 2016/03/09
SECONDARY ACCESSION(S): PRJNA314582
REPOSITORIES: GEO
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Project description:Nonsteroidal anti-inflammatory drugs (NSAIDs) has been suggested as adjunctive anti-tumor agents in human and veterinary medicine. However, its anti-tumor molecular machinery is still controversial. Therefore, we performed whole transcriptome analysis to discover gene expression influenced by NSAIDs treatment. A canine melanoma cell line (Mi/CMM1) was treated by three NSAIDs, piroxicam, carprofen, and robenacoxib, at their half maximal (50%) inhibitory concentrations (116 µM, 779 µM, and 156 µM) for 6 hours. Subsequently, total RNA were extracted and microarray analysis was performed to evaluate change in gene expression caused by NSAIDs treatment. Each condition had three biological replicates.
2016-03-09 | E-GEOD-78988 | biostudies-arrayexpress
Project description:Nonsteroidal anti-inflammatory drugs (NSAIDs), including salicylic acid (SA), target mammalian cyclooxygenases. In plants, SA is a defense hormone that regulates NON-EXPRESSOR OF PATHOGENESIS RELATED GENES 1 (NPR1), the master transcriptional regulator of immunity-related genes. We identify that the oxicam-type NSAIDs tenoxicam (TNX), meloxicam, and piroxicam, but not other types of NSAIDs, exhibit an inhibitory effect on immunity to bacteria and SA-dependent plant immune response. TNX treatment decreases NPR1 levels, independently from the proposed SA receptors NPR3 and NPR4. Instead, TNX induces oxidation of cytosolic redox status, which is also affected by SA and regulates NPR1 homeostasis. A cysteine labeling assay reveals that cysteine residues in NPR1 can be oxidized in vitro, leading to disulfide-bridged oligomerization of NPR1, but not in vivo regardless of SA or TNX treatment. Therefore, this study indicates that oxicam inhibits NPR1-mediated SA signaling without affecting the redox status of NPR1.
2021-11-09 | GSE154593 | GEO
Project description:Nonsteroidal anti-inflammatory drugs (NSAIDs), the quintessential medicines to treat pain and inflammatory conditions, induce cell death in human cancer cells, as repurposed anticancer agents, and in normal gastric mucosa, as a major side effect. The subcellular target/s of NSAIDs that leads to the cell death remained elusive so far. Here, by venturing transcriptomics followed by functional validation, we, for the first time, identified mitochondrial deacetylase Sirtuin 3 (Sirt3) as a non-canonical target of NSAIDs whose depletion induced the hyperacetylation of mitochondrial proteome, OGG1 depletion, mtDNA damage, electron transport chain defect associated mitochondrial dysfunction and finally cell death. Silencing of Sirt3 in AGS cells (a human gastric adenocarcinoma cell line) significantly aggravated NSAID-induced cytopathology. Whereas, honokiol mediated induction of Sirt3 corrected the NSAID-induced transcriptome alteration and gastropathy in rodent model. Together, the results identify Sirt3 as a common target used by NSAIDs to induce gastric carcinoma cell death and gastric mucosal injury.
2022-11-14 | GSE201565 | GEO
Project description:Nonsteroidal anti-inflammatory drugs (NSAIDs), the quintessential medicines to treat pain and inflammatory conditions, induce cell death in human cancer cells, as repurposed anticancer agents, and in normal gastric mucosa, as a major side effect. The subcellular target/s of NSAIDs that leads to the cell death remained elusive so far. Here, by venturing transcriptomics followed by functional validation, we, for the first time, identified mitochondrial deacetylase Sirtuin 3 (Sirt3) as a non-canonical target of NSAIDs whose depletion induced the hyperacetylation of mitochondrial proteome, OGG1 depletion, mtDNA damage, electron transport chain defect associated mitochondrial dysfunction and finally cell death. Silencing of Sirt3 in AGS cells (a human gastric adenocarcinoma cell line) significantly aggravated NSAID-induced cytopathology. Whereas, honokiol mediated induction of Sirt3 corrected the NSAID-induced transcriptome alteration and gastropathy in rodent model. Together, the results identify Sirt3 as a common target used by NSAIDs to induce gastric carcinoma cell death and gastric mucosal injury.
2022-11-14 | GSE202140 | GEO
Project description:Oxicam-type nonsteroidal anti-inflammatory drugs inhibit NPR1-mediated salicylic acid pathway
| PRJNA646744 | ENA
Project description:This study was undertaken to assess the similarities (or differences) between the well-established PPARγ agonist Rosiglitazone and Non-steroidal anti-inflammatory drugs (NSAIDs) diclofenac, indomethacin and ibuprofen, as well as the partial agonist GQ16 at the transcriptome level. Assessment of NSAID and GQ16 activities in PPARγ-dependent 3T3-L1 cells reveals that NSAIDs and GQ16 display similar effects toward PPARγ-dependent target genes in a manner similar to that of Rosiglitazone.
2015-06-01 | GSE64075 | GEO
Project description:Epidemiological studies have shown that the regular use of non-steroidal anti-inflammatory (NSAIDs) drugs is associated with a reduced risk of various cancers. In addition, in vitro and experiments in mouse models have demonstrated that NSAIDs decrease tumor initiation and/or progression of several cancers. However, there are limited preclinical studies investigating the effects of NSAIDs in ovarian cancer. Here, we have studied the effects of two NSAIDs, diclofenac and indomethacin, in ovarian cancer cell lines and in a xenograft mouse model. Diclofenac and indomethacin treatment decreased cell growth by inducing cell cycle arrest and apoptosis. In addition, diclofenac and indomethacin reduced tumor volume in a xenograft model of ovarian cancer. To identify possible molecular pathways mediating the effects of NSAID treatment in ovarian cancer, we performed microarray analysis of ovarian cancer cells treated with indomethacin or diclofenac. Interestingly, several of the genes found downregulated following diclofenac or indomethacin treatment are transcriptional target genes of E2F1. E2F1 was downregulated at the mRNA and protein level upon treatment with diclofenac and indomethacin, and overexpression of E2F1 rescued cells from the growth inhibitory effects of diclofenac and indomethacin. In conclusion, NSAIDs diclofenac and indomethacin exert an anti-proliferative effect in ovarian cancer in vitro and in vivo and the effects of NSAIDs may be mediated, in part, by downregulation of E2F1.
2014-06-20 | GSE45052 | GEO
Project description:Epidemiological studies have shown that the regular use of non-steroidal anti-inflammatory (NSAIDs) drugs is associated with a reduced risk of various cancers. In addition, in vitro and experiments in mouse models have demonstrated that NSAIDs decrease tumor initiation and/or progression of several cancers. However, there are limited preclinical studies investigating the effects of NSAIDs in ovarian cancer. Here, we have studied the effects of two NSAIDs, diclofenac and indomethacin, in ovarian cancer cell lines and in a xenograft mouse model. Diclofenac and indomethacin treatment decreased cell growth by inducing cell cycle arrest and apoptosis. In addition, diclofenac and indomethacin reduced tumor volume in a xenograft model of ovarian cancer. To identify possible molecular pathways mediating the effects of NSAID treatment in ovarian cancer, we performed microarray analysis of ovarian cancer cells treated with indomethacin or diclofenac. Interestingly, several of the genes found downregulated following diclofenac or indomethacin treatment are transcriptional target genes of E2F1. E2F1 was downregulated at the mRNA and protein level upon treatment with diclofenac and indomethacin, and overexpression of E2F1 rescued cells from the growth inhibitory effects of diclofenac and indomethacin. In conclusion, NSAIDs diclofenac and indomethacin exert an anti-proliferative effect in ovarian cancer in vitro and in vivo and the effects of NSAIDs may be mediated, in part, by downregulation of E2F1. The serous ovarian adenocarcinoma cell lines HEY, OVCAR5 and UCI-101 were grown in culture then seeded in 60 mm dishes and treated for 24 hours with 300 mM diclofenac, indomethacin or no treatment (Control). RNA was isolated and one sample from each group was labeled and hybridized to Illumina Sentrix bead arrays.
2014-06-20 | E-GEOD-45052 | biostudies-arrayexpress
Project description:<p><strong>BACKGROUND:</strong> Large-scale, placebo-controlled trials established that nonsteroidal anti-inflammatory drugs confer a cardiovascular hazard: this has been attributed to depression of cardioprotective products of cyclooxygenase (COX)-2, especially prostacyclin. An alternative mechanism by which nonsteroidal anti-inflammatory drugs might constrain cardioprotection is by enhancing the formation of methylarginines in the kidney that would limit the action of nitric oxide throughout the vasculature.</p><p><strong>METHODS:</strong> Targeted and untargeted metabolomics were used to investigate the effect of COX-2 deletion or inhibition in mice and in osteoarthritis patients exposed to nonsteroidal anti-inflammatory drugs on the l-arginine/nitric oxide pathway.</p><p><strong>RESULTS:</strong> Analysis of the plasma and renal metabolome was performed in postnatal tamoxifen-inducible Cox-2 knockout mice, which exhibit normal renal function and blood pressure. This revealed no changes in arginine and methylarginines compared with their wild-type controls. Moreover, the expression of genes in the l-arginine/nitric oxide pathway was not altered in the renal medulla or cortex of tamoxifen inducible Cox-2 knockout mice. Therapeutic concentrations of the selective COX-2 inhibitors, rofecoxib, celecoxib, and parecoxib, none of which altered basal blood pressure or renal function as reflected by plasma creatinine, failed to elevate plasma arginine and methylarginines in mice. Finally, plasma arginine or methylarginines were not altered in osteoarthritis patients with confirmed exposure to nonsteroidal anti-inflammatory drugs that inhibit COX-1 and COX-2. By contrast, plasma asymmetrical dimethylarginine was increased in mice infused with angiotensin II sufficient to elevate blood pressure and impair renal function. Four weeks later, blood pressure, plasma creatinine, and asymmetrical dimethylarginine were restored to normal levels. The increase in asymmetrical dimethylarginine in response to infusion with angiotensin II in celecoxib-treated mice was also related to transient impairment of renal function.</p><p><strong>CONCLUSIONS:</strong> Plasma methylarginines are not altered by COX-2 deletion or inhibition but rather are elevated coincident with renal compromise.</p><p><br></p><p><strong>Murine kidney and plasma UPLC-MS/MS assay</strong> protocols and data are reported in the current study <strong>MTBLS680</strong>.</p><p><strong>Murine and human plasma quantitative L-arginine and methylarginines UPLC-MS/MS assay</strong> protocols and data are reported in <a href="https://www.ebi.ac.uk/metabolights/MTBLS685" target="_blank"><strong>MTBLS685</strong></a>.</p>
2019-08-22 | MTBLS680 | MetaboLights
Project description: Not available
| S-EPMC6340804 | biostudies-other