Effect of PY-ITC and sulforaphane on gene expression of PC3 and PNT1A prostate cells in the presence and absence of the PI3K inhibitor LY294002
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
DISEASE(S): prostate cancer
SUBMITTER: Maria Traka
PROVIDER: E-MEXP-3640 | biostudies-arrayexpress |
REPOSITORIES: biostudies-arrayexpress
Similar Datasets
Project description:Background: Earthworms are essential for a healthy soil ecosystem, performing key functions such as bioturbation. The soil ecosystem can be challenged by natural toxins such as isothiocyanates (ITC), secondary metabolites produced by many commercial crops. This study investigated the effects of the natural toxin, 2-phenylethyl isothiocyanate on the earthworm Eisenia andrei using an ecotoxicogenomics approach that combined standardised ecotoxicological testing with gene expression analyses. Results and discussion: Exposure to 2-Phenylethyl ITC reduced both survival and reproduction of E. andrei in a dose-dependent manner, with an EC50 (reproduction) value of 556 nmol/g soil. Cross-species comparative genomic hybridisation validated the applicability of an existing 4x44k E. fetida microarray to E. andrei. Gene expression profiles revealed the importance of metallothionein (mt) as an early warning signal when E. andrei is exposed to low concentrations of 2-phenylethyl ITC. Allignment of these mt genes with the mt-2 gene of Lumbricus rubellus showed that there must at least have 2 mt genes in the Eisenia sp. genome. At high exposure concentrations of 2-phenylethyl ITC gene expression was mainly affected by inhibiting chitinase activities, inducing an oxidative stress response, and stimulating energy metabolism. KEGG pathway analysis, furthermore, implied that the high concentration may cause impaired light sensitivity, angiogenesis (e.g. wound healing), olfactory perception (olfaction), learning and memory. Conclusions: Increased levels of isothiocyanates may be found in the field in the near future. Risks of such compounds should be carefully investigated before allowing them to enter the soil on a large scale. This is the first study to investigate the effects of an isothiocyanate on an earthworm both on the ecotoxicological and genomic level.
2013-08-11 | GSE43600 | GEO
Project description:Background: Earthworms are essential for a healthy soil ecosystem, performing key functions such as bioturbation. The soil ecosystem can be challenged by natural toxins such as isothiocyanates (ITC), secondary metabolites produced by many commercial crops. This study investigated the effects of the natural toxin, 2-phenylethyl isothiocyanate on the earthworm Eisenia andrei using an ecotoxicogenomics approach that combined standardised ecotoxicological testing with gene expression analyses. Results and discussion: Exposure to 2-Phenylethyl ITC reduced both survival and reproduction of E. andrei in a dose-dependent manner, with an EC50 (reproduction) value of 556 nmol/g soil. Cross-species comparative genomic hybridisation validated the applicability of an existing 4x44k E. fetida microarray to E. andrei. Gene expression profiles revealed the importance of metallothionein (mt) as an early warning signal when E. andrei is exposed to low concentrations of 2-phenylethyl ITC. Allignment of these mt genes with the mt-2 gene of Lumbricus rubellus showed that there must at least have 2 mt genes in the Eisenia sp. genome. At high exposure concentrations of 2-phenylethyl ITC gene expression was mainly affected by inhibiting chitinase activities, inducing an oxidative stress response, and stimulating energy metabolism. KEGG pathway analysis, furthermore, implied that the high concentration may cause impaired light sensitivity, angiogenesis (e.g. wound healing), olfactory perception (olfaction), learning and memory. Conclusions: Increased levels of isothiocyanates may be found in the field in the near future. Risks of such compounds should be carefully investigated before allowing them to enter the soil on a large scale. This is the first study to investigate the effects of an isothiocyanate on an earthworm both on the ecotoxicological and genomic level. Three-exposure experiment; Acetone control vs.EC10 vs.EC50 exposed animals. Biological replicates: 4 replicates for each exposure. Technical replicates: 2 replicates for each exposure
2013-08-11 | E-GEOD-43600 | biostudies-arrayexpress
Project description:Single-cell RNA-seq (scRNA-seq) on nocodazole and DMSO treated cells before and after differentiation into endoderm. hPSC colonies were treated with DMSO or 100ng/ml nocodazole for 16 hours and induced to differentiate into definitive endoderm for three days. Single cells were subsequently collected in either undifferentiated conditions (Und) or after 3 days of endoderm differentiation (Endoderm) and then sorted onto 384 well plates for Smart-Seq2 processing.
2019-02-09 | E-MTAB-7008 | biostudies-arrayexpress
Project description:BACKGROUND: Broccoli consumption has been associated with a reduction in risk of prostate cancer. Isothiocyanates (ITC) derived from glucosinolates that accumulate in broccoli are potential dietary compounds that may mediate these health effects. Sulforaphane (SF, 4-methylsulphinylbutyl ITC) accumulates in heading broccoli (calabrese) and iberin (IB, 3-methylsulphinypropyl ITC) accumulates in sprouting broccoli. While, there are many studies regarding the biological activity of SF, there are few studies associated with IB. Moreover, the majority of studies have been undertaken with transformed cells, usually epithelial in origin, that have cancerous phenotypes. <br>METHOD: Primary epithelial and stromal cells were derived from benign prostatic hyperplasia tissue. Affymetrix U133 Plus 2.0 whole genome arrays were used to quantify global gene expression changes in these cells, following exposure to physiologically appropriate concentrations of SF and IB. Ontology and pathway analyses were used to interpret results. Changes in expression of a subset of genes were confirmed by RT PCR.<br>RESULTS: Global gene expression profiling identified epithelial and stromal specific gene expression profiles. IB and SF induced different changes in gene expression in both epithelial and stromal cells but these changes were associated with similar functions<br>CONCLUSION: This data suggests that IB and SF both induce genes associated with cancer prevention, and IB should be further investigated as a potential chemo-preventative target. <br>
2009-06-05 | E-MEXP-2034 | biostudies-arrayexpress
Project description:Natural toxins, such as isothiocyanate (ITC), are harmful secondary metabolites produced by plants. Many natural toxins occur in commercial crops, yet their possible negative repercussions on especially non-target soil organisms are largely unknown. This study examined molecular effects of 2-phenylethyl ITC on the soil arthropod species: Folsomia candida. Complementing ecotoxicological experiments with gene expression profiling allows the study of the underlying modes of action of toxins. For this the standardized ISO guideline for ecotoxicological experiments and a microarray for F. candida (GPL7150) were used. Toxic effects on reproduction were shown for F. candida, with EC50 values of around 11.5 nmol/g soil, illustrating the toxic character of this compound. A total of 130 genes were significantly differentially expressed between C and AC. The compounds were spiked in with acetone and due to the substantial difference between the two controls, only AC was chosen for further contrast analysis, comparing AC to EC10 and EC50 gene expressions. At EC10 level, 75 genes and at the EC50 level 107 genes were differentially expressed compared to AC. Approximately 36% of all significant genes could be annotated using Blast2GO. Gene expression profiles revealed the importance of lipid metabolism at low exposure concentrations (EC10), which is associated with the lipophilic nature of 2-phenylethyl ITC. At higher dosages (EC50) a wider array of genes was over-expressed, which included genes related to stress and sugar metabolism. Our study provides new insights in the molecular mode of action of a natural toxin soil animals. This study is the first step towards an understanding of these potential risks by studying the effects of a natural toxin at a life-history trait and molecular level. Four-exposure experiment; Control vs. Acetone control vs.EC10 vs.EC50 exposed animals. Biological replicates: 4 replicates for each exposure.
2011-12-29 | E-GEOD-26698 | biostudies-arrayexpress
Project description:In tumor cells, stepwise oncogenic deregulation of signaling cascades induces alterations of cellular morphology and promotes the acquisition of malignant traits. Using a panel of small molecular inhibitors, we established associated gene expression signatures of key signaling hubs. SW480 cells were grown in DMEM, 10% FCS, and treated for 24h with the following inhibitors or with solvent (DMSO): SU5402 (42uM); U0126 (10uM), SP600125 (20uM), LY294002 (20uM)
2011-06-03 | E-GEOD-29689 | biostudies-arrayexpress
Project description:Natural toxins, such as isothiocyanate (ITC), are harmful secondary metabolites produced by plants. Many natural toxins occur in commercial crops, yet their possible negative repercussions on especially non-target soil organisms are largely unknown. This study examined molecular effects of 2-phenylethyl ITC on the soil arthropod species: Folsomia candida. Complementing ecotoxicological experiments with gene expression profiling allows the study of the underlying modes of action of toxins. For this the standardized ISO guideline for ecotoxicological experiments and a microarray for F. candida (GPL7150) were used. Toxic effects on reproduction were shown for F. candida, with EC50 values of around 11.5 nmol/g soil, illustrating the toxic character of this compound. A total of 130 genes were significantly differentially expressed between C and AC. The compounds were spiked in with acetone and due to the substantial difference between the two controls, only AC was chosen for further contrast analysis, comparing AC to EC10 and EC50 gene expressions. At EC10 level, 75 genes and at the EC50 level 107 genes were differentially expressed compared to AC. Approximately 36% of all significant genes could be annotated using Blast2GO. Gene expression profiles revealed the importance of lipid metabolism at low exposure concentrations (EC10), which is associated with the lipophilic nature of 2-phenylethyl ITC. At higher dosages (EC50) a wider array of genes was over-expressed, which included genes related to stress and sugar metabolism. Our study provides new insights in the molecular mode of action of a natural toxin soil animals. This study is the first step towards an understanding of these potential risks by studying the effects of a natural toxin at a life-history trait and molecular level.
2011-12-29 | GSE26698 | GEO
Project description:Natural toxins, such as isothiocyanate (ITC), are harmful secondary metabolites produced by plants. Many natural toxins occur in commercial crops, yet their possible negative repercussions on especially non-target soil organisms are largely unknown. This study examined molecular effects of 2-phenylethyl ITC on the soil arthropod species: Folsomia candida. Complementing ecotoxicological experiments with gene expression profiling allows the study of the underlying modes of action of toxins. For this the standardized ISO guideline for ecotoxicological experiments and a microarray for F. candida (GPL7150) were used. Toxic effects on reproduction were shown for F. candida, with EC50 values of around 11.5 nmol/g soil, illustrating the toxic character of this compound. A total of 130 genes were significantly differentially expressed between C and AC. The compounds were spiked in with acetone and due to the substantial difference between the two controls, only AC was chosen for further contrast analysis, comparing AC to EC10 and EC50 gene expressions. At EC10 level, 75 genes and at the EC50 level 107 genes were differentially expressed compared to AC. Approximately 36% of all significant genes could be annotated using Blast2GO. Gene expression profiles revealed the importance of lipid metabolism at low exposure concentrations (EC10), which is associated with the lipophilic nature of 2-phenylethyl ITC. At higher dosages (EC50) a wider array of genes was over-expressed, which included genes related to stress and sugar metabolism. Our study provides new insights in the molecular mode of action of a natural toxin soil animals. This study is the first step towards an understanding of these potential risks by studying the effects of a natural toxin at a life-history trait and molecular level.
2011-05-12 | GSE29239 | GEO
Project description:Natural toxins, such as isothiocyanate (ITC), are harmful secondary metabolites produced by plants. Many natural toxins occur in commercial crops, yet their possible negative repercussions on especially non-target soil organisms are largely unknown. This study examined molecular effects of 2-phenylethyl ITC on the soil arthropod species: Folsomia candida. Complementing ecotoxicological experiments with gene expression profiling allows the study of the underlying modes of action of toxins. For this the standardized ISO guideline for ecotoxicological experiments and a microarray for F. candida (GPL7150) were used. Toxic effects on reproduction were shown for F. candida, with EC50 values of around 11.5 nmol/g soil, illustrating the toxic character of this compound. A total of 130 genes were significantly differentially expressed between C and AC. The compounds were spiked in with acetone and due to the substantial difference between the two controls, only AC was chosen for further contrast analysis, comparing AC to EC10 and EC50 gene expressions. At EC10 level, 75 genes and at the EC50 level 107 genes were differentially expressed compared to AC. Approximately 36% of all significant genes could be annotated using Blast2GO. Gene expression profiles revealed the importance of lipid metabolism at low exposure concentrations (EC10), which is associated with the lipophilic nature of 2-phenylethyl ITC. At higher dosages (EC50) a wider array of genes was over-expressed, which included genes related to stress and sugar metabolism. Our study provides new insights in the molecular mode of action of a natural toxin soil animals. This study is the first step towards an understanding of these potential risks by studying the effects of a natural toxin at a life-history trait and molecular level. Four-exposure experiment; Control vs. Acetone control vs.EC10 vs.EC50 exposed animals. Biological replicates: 4 replicates for each exposure.
2011-05-12 | E-GEOD-29239 | biostudies-arrayexpress
Project description:Transcription factors belonging to the same transcription factor families contain very similar DNA binding domains and hence have the potential to bind to related DNA sequences. However subtle differences in binding specificities can be detected in vitro with the potential to direct specific responses in vivo. In this study the binding properties of three Forkhead transcription factors, FOXK2, FOXO3 and FOXJ3 were studied in vivo. Here we submit the gene expression component of this study. LY294002 treatment of U2OS cells which promotes FOXO3 translocation to the nucleus, and hence activation of the FOXO3 target genes.
2016-01-20 | E-MTAB-3763 | biostudies-arrayexpress