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Project description:Salinomycin treatment of Alisertib induced senescent A549 cells
| PRJNA1171320 | ENA
Project description:Cancer stem cells are believed to play a crucial role in cancer recurrence due to their resistance to conventional chemotherapy and capacity for self-renewal. Recent studies have reported that salinomycin, a livestock antibiotic, selectively targets breast cancer stem cells 100-fold more effectively than paclitaxel. In our study we sought to determine the effects of salinomycin on head and neck squamous cell carcinoma (HNSCC) stem cells. We show that salinomycin is able to decrease cell viability and induce apoptosis. In combination with the chemotherapeutic agents cisplatin and paclitaxel, salinomycin synergistically killed HNSCC cancer stem cells more effectively than either drug alone. Furthermore, we observed that salinomycin decreases stem cell properties as shown by a significant reduction in sphere formation and a decrease of both CD44 and BMI-1. Contrary to expectations, salinomycin caused an induction of EMT as shown by an increase in Snail and Vimentin, and a decrease in E-cadherin expression. Even though EMT was induced, salinomycin caused a decrease in invasion through a membrane. In search of a possible mechanism, the effects on the Akt pathway were explored. Interestingly, salinomycin also induced phosphorylation of Akt. Activation of EMT and Akt are both tightly associated with an increase in stemness, which brings to question the relationship between CSCs and these two fundamental pathways. Taken together, our findings indicate that salinomycin shows promise as a novel treatment for HNSCC despite an activation of EMT and Akt. MicroRNA obtained from JLO-1 cells treated for 48 hours in varying doses of salinomycin. Changes in microRNA expression are analyzed by normalizing expression values with the control sample.
2013-12-31 | E-GEOD-33196 | biostudies-arrayexpress
Project description:Epithelial-to-mesenchymal transition (EMT) gives rise to cells with properties similar to cancer stem cells (CSCs) that drive tumor metastasis. Recently, a screening of a large compound library on a breast EMT model has identified salinomycin, a K+/H+ ionophore, as a highly selective drug towards CSCs. We used the same EMT model to show that salinomycin targets Golgi apparatus. We have performed RNA-seq analysis on HMLE-Twist and HMLE-pBp cells (EMT and non-EMT) that were either mock treated or treated for 24h with micro molar concentration (0.2uM) of salinomycin. Salinomycin induced expression of genes enriched by known ER and Golgi stressors.
2023-01-11 | GSE124975 | GEO
Project description:Streptomyces albus S12, TK and Tet30Chl25 are the parental strain , low-yield and high-yield of salinomycin mutant obtained by ARTP and ribosome engineering ,respectively. There are total 1602 differentially expressed genes (DEGs) show differences in expression between the mutant strain TK, Tet30Chl25 and the initial strain S12. KEGG pathway analysis of differentially expressed genes (DEGs) between the mutant strain TK, Tet30Chl25 and the initial strain S12 show that the relevant differential pathways affecting salinomycin production were mainly related to butanoate metabolism, starch and sucrose metabolism, glyoxylate metabolism. Besides , the transcription of genes in the salinomycin biosynthesis gene cluster and the transcription level of related genes in the precursors biosynthesis pathway were more active in the high-yield salinomycin production strain Tet30Chl25. Furthermore, the transcription level ribosomal protein, string response, two component system and sigma factors are more active in high-yield of salinomycin mutants and that may involve in regulation of salinomycin biosynthesis and may account for the high-yield of salinomycin.
2019-10-01 | GSE133580 | GEO
Project description:Screens for agents that specifically kill epithelial cancer stem cells (CSCs) have not been possible due to the rarity of these cells within tumor cell populations and their relative instability in culture. We describe here an approach to screening for agents with epithelial CSC-specific toxicity. We implemented this method in a chemical screen and discovered compounds showing selective toxicity for breast CSCs. One compound, salinomycin, reduces the proportion of CSCs by >100-fold relative to paclitaxel, a commonly used breast cancer chemotherapeutic drug. Treatment of mice with salinomycin inhibits mammary tumor growth in vivo and induces increased epithelial differentiation of tumor cells. In addition, global gene expression analyses show that salinomycin treatment results in the loss of expression of breast CSC genes previously identified by analyses of breast tissues isolated directly from patients. This study demonstrates the ability to identify agents with specific toxicity for epithelial CSCs Experiment Overall Design: Experimentally transformed HMLER breast cancer cells were treated in culture with either paclitaxel (10nM) or salinomycin (1uM) for one week. There were three biologic replicates for each treatment condition.
2009-09-15 | E-GEOD-17215 | biostudies-arrayexpress
Project description:Cancer stem cells are believed to play a crucial role in cancer recurrence due to their resistance to conventional chemotherapy and capacity for self-renewal. Recent studies have reported that salinomycin, a livestock antibiotic, selectively targets breast cancer stem cells 100-fold more effectively than paclitaxel. In our study we sought to determine the effects of salinomycin on head and neck squamous cell carcinoma (HNSCC) stem cells. We show that salinomycin is able to decrease cell viability and induce apoptosis. In combination with the chemotherapeutic agents cisplatin and paclitaxel, salinomycin synergistically killed HNSCC cancer stem cells more effectively than either drug alone. Furthermore, we observed that salinomycin decreases stem cell properties as shown by a significant reduction in sphere formation and a decrease of both CD44 and BMI-1. Contrary to expectations, salinomycin caused an induction of EMT as shown by an increase in Snail and Vimentin, and a decrease in E-cadherin expression. Even though EMT was induced, salinomycin caused a decrease in invasion through a membrane. In search of a possible mechanism, the effects on the Akt pathway were explored. Interestingly, salinomycin also induced phosphorylation of Akt. Activation of EMT and Akt are both tightly associated with an increase in stemness, which brings to question the relationship between CSCs and these two fundamental pathways. Taken together, our findings indicate that salinomycin shows promise as a novel treatment for HNSCC despite an activation of EMT and Akt.
2013-12-31 | GSE33196 | GEO
Project description:Screens for agents that specifically kill epithelial cancer stem cells (CSCs) have not been possible due to the rarity of these cells within tumor cell populations and their relative instability in culture. We describe here an approach to screening for agents with epithelial CSC-specific toxicity. We implemented this method in a chemical screen and discovered compounds showing selective toxicity for breast CSCs. One compound, salinomycin, reduces the proportion of CSCs by >100-fold relative to paclitaxel, a commonly used breast cancer chemotherapeutic drug. Treatment of mice with salinomycin inhibits mammary tumor growth in vivo and induces increased epithelial differentiation of tumor cells. In addition, global gene expression analyses show that salinomycin treatment results in the loss of expression of breast CSC genes previously identified by analyses of breast tissues isolated directly from patients. This study demonstrates the ability to identify agents with specific toxicity for epithelial CSCs
2009-08-20 | GSE17215 | GEO
Project description:RNA sequencing was performed on MDA-MB-231 samples treated with TGFβ nad Alisertib to obtaine the TGFβ-mediated gene expression profile which is regulated by AURKA activity.
2020-12-31 | GSE160990 | GEO
Project description:The presence of senescent cells in the aging/degenerating human disc is now well-recognized. Senescent cells are viable, cannot divide, remain metabolically active and accumulate within the disc over time. Molecular analysis of senescent cells in tissue, however, offers a special challenge since there are no cell surface markers for senescence which would let one use fluorescence-activated cell sorting as a method for separating out senescent cells. Here we use a novel experimental design using laser capture microdissection to selectively separately harvest senescent and non-senescent annulus cells in paraffin-embedded tissue, and then compare their gene expression with microarray analysis. An initial in vitro study using cultured human annulus cells was first performed to test whether there was any difference in identification of senescent cells using the accepted histochemical methodology vs. the immunofluoresent identification of cells positive for senescence-associated-ß-galactosidase in control cells and cells induced into stress-induced premature senescence via hydrogen peroxide exposure. No statistically significant difference was found between the 2 methods. Laser capture microdissection was used to separately harvest senescent and non-senescent cells from 11 human annulus specimens, and microarray analysis was used to determine gene expression levels. Genes with established relationships to senescence were found to be significantly upregulated in senescent cells vs. non-senescent cells. Additional genes related to cytokines, cell proliferation, and other cell processes were also identified. Disc Tissue samples were obtained from surgical disc procedures performed on patients with herniated discs and degenerative disc disease. Tissue was fixed and paraffin embedded. Standard laser capture microdissection (LCM) techniques were used to collect senescent cells. Remaining non-senescent cells were scraped from the histology slide. Total RNA was isolated and analyzed via mircoarray. Gene expression from senescent cells was compared to non-senescent cells. Eight histological samples were used to obtain both senescent and non-senescent cells. From an additional 3 samples, only senescent cells were harvested.
2009-07-15 | E-GEOD-17077 | biostudies-arrayexpress
Project description:Transcriptional profiling of senescent A549 cells
| PRJNA656112 | ENA