Colon cancer shperes are sensitive to Fenretinide
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE66983 | GEO | 2016/04/03
SECONDARY ACCESSION(S): PRJNA278631
REPOSITORIES: GEO
Similar Datasets
Project description:Fenretinide has shown its antitumor activity in many tumor types with low cytotoxicity to normal cells. Recently, we have shown that fenretinide could eradicate chronic myeloid leukemia stem/progenitor cells and spheres from ovarian cancer. In this study, we investigate whether fenretinide could selectively target sphere cells of colon cancer. Using high-throughtput microarray system, we identified GO terms and pathway signatures enriched in fenretinide treated HT29 cells and HT29 derived sphere cells. Colon cancer cells HT29 were cultured in sphere formation conditions, HT29 cells and HT29 derived sphere cells were treated with fenretinide, and total RNA from those spheres and corresponding adhered cell was hybridized on Affymetrix U133 plus 2.0 genechip.
2016-04-03 | E-GEOD-66983 | biostudies-arrayexpress
Project description:Transcriptional profiling of human acute myelogenous leukemia (AML) CD34+ cells treated with 5 μM fenretinide. Two timepoints included are 6h, 12h, covering the apoptosis-induction time window of AML CD34+ cells responsing to the fenretinide treatment. We studied gene expression series in human AML CD34+ cells with or without 5 μM fenretinide treatment by cDNA microarray analysis. Several signal transduction pathways are involve, including stress response, NF-kappaB inhibition and p53 inhibition (p<0.05). These findings indicate fenretinide may represent a promising candidate for targeting AML-initiating cells.
2011-11-30 | GSE33243 | GEO
Project description:Imatinib, as the first-line agent of chronic myeloid leukemia (CML), is ineffective in eradicating CML stem/progenitor cells, thus unable to prevent late relapse. Here we present data indicating that fenretinide preferentially targets CD34+ CML cells and enhances the efficacy of imatinib in CML. As tested by colony forming cell assays, both number and size of total colonies derived from CD34+ CML cells were significantly reduced by fenretinide, and by combining fenretinide with imatinib. In particular, colonies derived from erythroid progenitors and those derived from more primitive pluripotent progenitor cells were highly sensitive to fenretinide/fenretinide plus immtinib. Further data showed that fenretinide was able to induce apoptosis in CD34+ CML cells which were refractory to imatinib. Through transcriptome analysis and followed by molecular validation, we further showed that apoptosis induced by fenretinide in CD34+ CML cells was mediated by complex mechanisms of stress responses, probably triggered by elevated levels of intracellular reactive oxygen species. Thus, fenretinide combines with imatinib may represent a new strategy for the treatment of CML, in which fenretinide targets primitive CD34+ CML cells whereas imatinib targets leukemic blasts. This strategy may eventually reduce the risk of relapse and probably resistant as well in CML patients.
2009-12-01 | GSE17480 | GEO
Project description:Transcriptional profiling of human acute myelogenous leukemia (AML) CD34+ cells treated with 5 μM fenretinide. Two timepoints included are 6h, 12h, covering the apoptosis-induction time window of AML CD34+ cells responsing to the fenretinide treatment. We studied gene expression series in human AML CD34+ cells with or without 5 μM fenretinide treatment by cDNA microarray analysis. Several signal transduction pathways are involve, including stress response, NF-kappaB inhibition and p53 inhibition (p<0.05). These findings indicate fenretinide may represent a promising candidate for targeting AML-initiating cells. 6-condition experiment, untreated AML CD34+ cells vs. fenretinide-treated AML CD34+ cells,including 2 time points, for each point the untreated and 5 μM fenretinide treated, independently grown and harvested. Untreated was used to counteracting the background.
2011-11-30 | E-GEOD-33243 | biostudies-arrayexpress
Project description:Imatinib therapy is first-line treatment for chronic myeloid leukemia (CML), and its failure to target CML progenitor/stem cells may lead to an increased risk of relapse. We report here that fenretinide, a well-tolerated vitamin A derivative, is capable of eradicating primitive CML progenitor/stem cells and significantly enhances the efficacy of imatinib at physiologically achievable concentrations. As tested by colony forming cell assays, formation of various colonies derived primitive CML CD34+ cells was significantly suppressed by fenretinide, particularly with respect to the formation of colonies derived from erythroid progenitors and more primitive CML progenitor/stem cells. Also, fenretinide significantly enhanced the ability of imatinib to suppress the formation of the colonies. Moreover, fenretinide was able to induce apoptosis in primitive CML CD34+ cells while sparing the normal counterparts. In particular, primitive CML CD34+CD38- cells appeared to be most sensitive to fenretinide induced apoptosis. Through transcriptome analysis and molecular validation, we further showed that fenretinide induced apoptosis in CML CD34+ cells was probably mediated by a series of stress responsive events which were likely triggered by elevated levels of intracellular reactive oxygen species. Accordingly, the combination of fenretinide and imatinib may provide a potential solution for overcoming relapse and resistance in CML. Experiment Overall Design: Transcriptome profiles of CML CD34+ cells with and without fenretinide treatment were analyzed using whole genome expression arrays (Affymetrix HG-U133 Plus 2.0) in four CML patients (CML32, CML33, CML34 and CML35, see Table 1). To minimize potential data biases, both treated and untreated cell samples were maintained in culture for 48 hours before hybridization.
2009-12-05 | E-GEOD-17480 | biostudies-arrayexpress
Project description:The identification and characterization of subpopulations of cancer stem cells (CSCs) provide new understandings and possible therapeutic implications in cancer biology. We found the ovarian cancer sphere cells possessed CSCs properties maintained self renewal, drug resistance, and tumorigenesis. Using high-throughput microarray system, we identified common GO terms and pathway signatures significantly enriched in ovarian and breast cancer stem cells.
2013-11-25 | GSE43657 | GEO
Project description:Pharmacological intervention of redox balance in cancer cells often results in oxidative stress-mediated apoptosis, attracting much attention for the development of a new generation of targeted therapy in cancer. However, little is known about mechanisms underlying the conversion from oxidative signaling to downstream activities leading cells to death. We here report a systematic detection of transcriptome changes in response to oxidative signals generated in leukemia cells upon fenretinide treatment, implicating the occurrence of numerous stress-responsive events during the fenretinide induced apoptosis, such as redox response, endoplasmic reticulum stress/unfolded protein response, translational repression and proteasome activation. Moreover, the configuration of these relevant events is primarily orchestrated by stress responsive transcription factors, as typically highlighted by NF-E2-related factor-2 (NRF2) and heat shock factor 1 (HSF1). Several lines of evidence suggest that the coordinated regulation of these transcription factors and thus their downstream genes are involved in converting oxidative signaling into downstream stress-responsive events regulating pro-apoptotic and apoptotic activities at the temporal and spatial levels, typifying oxidative stress-mediated programmed death rather than survival in cancer cells. This study provides a roadmap for understanding oxidative stress-mediated apoptosis in cancer cells, which may be further developed into more sophisticated therapeutic protocols, as implicated by synergistic induction of cell apoptosis using proteasome inhibitors with fenretinide.
2009-09-15 | GSE16578 | GEO
Project description:Pharmacological intervention of redox balance in cancer cells often results in oxidative stress-mediated apoptosis, attracting much attention for the development of a new generation of targeted therapy in cancer. However, little is known about mechanisms underlying the conversion from oxidative signaling to downstream activities leading cells to death. We here report a systematic detection of transcriptome changes in response to oxidative signals generated in leukemia cells upon fenretinide treatment, implicating the occurrence of numerous stress-responsive events during the fenretinide induced apoptosis, such as redox response, endoplasmic reticulum stress/unfolded protein response, translational repression and proteasome activation. Moreover, the configuration of these relevant events is primarily orchestrated by stress responsive transcription factors, as typically highlighted by NF-E2-related factor-2 (NRF2) and heat shock factor 1 (HSF1). Several lines of evidence suggest that the coordinated regulation of these transcription factors and thus their downstream genes are involved in converting oxidative signaling into downstream stress-responsive events regulating pro-apoptotic and apoptotic activities at the temporal and spatial levels, typifying oxidative stress-mediated programmed death rather than survival in cancer cells. This study provides a roadmap for understanding oxidative stress-mediated apoptosis in cancer cells, which may be further developed into more sophisticated therapeutic protocols, as implicated by synergistic induction of cell apoptosis using proteasome inhibitors with fenretinide. Time-series experiment, fenretinide treated NB4 cells at 19 time points (i.e., 0.25, 0.5, 1, 2, 4, 6, 8, 10, 12, 15, 18, 21, 24, 30, 36, 42, 48, 54 and 60 hours) and untreated NB4 cells at 4 time points (i.e., 0, 8, 12 and 15 hours).
2010-05-05 | E-GEOD-16578 | biostudies-arrayexpress
Project description:The tumor microenvironment is highly complex and consists af many non-tumor cells and factors. To simplify the complexity, we developed a simple in vitro system where tumor (neuroblastoma) 'spheres' ~1-2 mm in diameter were generated on concave surfaces of noble agar. After sphere development, bone marrow-derived macrophages were added to the well. Many macrophages crawled into the spheres (as shown by live cell microscopy). After 24-28 h, the macrophages were isolated from inside or outside the tumor spheres using tissue digestion and anti-CD11b MACs beads. The macrophages from inside or outside the spheres were then subject to microarray analysis.
2016-05-02 | GSE68817 | GEO
Project description:Specification to primordial germ cells (PGCs) occurs under the mesoderm induction signals during gastrulation. Here, we found that Akt activation in embryonic stem (ES) cells generated self-renewing spheres during mesodermal differentiation induction and that the differentiation status of the sphere cells was in between ES cells and PGCs. Essential regulators for PGC specification and their downstream germ cell-specific genes were expressed in the spheres, showing that the cells of the sphere commenced the differentiation to germ lineage. However, the spheres could not proceed to spermatogenesis after transplantation to testes. Meanwhile, the transfer of the spheres to the original feeder-free ES cell culture conditions induced chaotic differentiation. In contrast, when the spheres were cultured on mouse embryonic fibroblasts or in the presence of ERK-cascade and GSK3 inhibitors, the reversion to the ES cell-like cell states was induced. These results indicate that the Akt signaling brings about a novel metastable and pluripotent state between ES cells and PGCs. Five samples were analyzed, which included the Akt-Mer-expressing ES cell (ESC) line #21 treated with or without 4OHT (4-hydroxytamoxifen), the #21 ESC-derived primordial germ cell (PGC)-like sphere cells and the ESC-like cells reverted from #21 PGC-like sphere cells. The PGC-like sphere cells derived from another Akt-Mer ESC line #42 was also examined.
2010-04-30 | E-GEOD-18813 | biostudies-arrayexpress