Inhibitory effect of shikonin on lung cancer cells
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE222640 | GEO | 2024/01/10
REPOSITORIES: GEO
Similar Datasets
Project description:Non-small cell lung cancer (NSCLC) is the most lethal and prevalent type of lung cancer. In almost all types of cancer, the levels of polyamines (putrescine, spermidine, and spermine) are increased, playing a pivotal role in tumor proliferation. Indomethacin, a non-steroidal anti-inflammatory drug, increases the abundance of an enzyme termed spermidine/spermine-N1-acetyltransferase (SSAT) encoded by the SAT1 gene. This enzyme is a key player in the export of polyamines from the cell. The aim of this study was to compare the effect of indomethacin on two NSCLC cell lines, and their combinatory potential with polyamine-inhibitor drugs in NSCLC cell lines. A549 and H1299 NSCLC cells were exposed to indomethacin and evaluations included SAT1 expression, SSAT levels, and the metabolic status of cells. Moreover, the difference in polyamine synthesis enzymes among these cell lines as well as the synergistic effect of indomethacin and chemical inhibitors of the polyamine pathway enzymes on cell viability were investigated. Indomethacin increased the expression of SAT1 and levels of SSAT in both cell lines. In A549 cells, it significantly reduced the levels of putrescine and spermidine. However, in H1299 cells, the impact of treatment on the polyamine pathway was insignificant. Also, the metabolic features upstream of the polyamine pathway (i.e., ornithine and methionine) were increased. In A549 cells, the increase of ornithine correlated with the increase of several metabolites involved in the urea cycle. Evaluation of the levels of the polyamine synthesis enzymes showed that ornithine decarboxylase is increased in A549 cells, whereas S-adenosylmethionine-decarboxylase and polyamine oxidase are increased in H1299 cells. This observation correlated with relative resistance to polyamine synthesis inhibitors eflornithine and SAM486 (inhibitors of ornithine decarboxylase and S-adenosyl-L-methionine decarboxylase, respectively), and MDL72527 (inhibitor of polyamine oxidase and spermine oxidase). Finally, indomethacin demonstrated a synergistic effect with MDL72527 in A549 cells and SAM486 in H1299 cells. Collectively, these results indicate that indomethacin alters polyamine metabolism in NSCLC cells and enhances the effect of polyamine synthesis inhibitors, such as MDL72527 or SAM486. However, this effect varies depending on the basal metabolic fingerprint of each type of cancer cell.
2021-02-08 | MTBLS873 | MetaboLights
Project description:Minichromosome maintenance protein 2 (MCM2) is a licensing factor for DNA replication. It interacts with other MCM proteins to comprise MCM2-7 complex, which acts as a helicase for DNA unwinding and limits DNA replication to one round per cell cycle. MCM2 has been widely used as a biomarker for proliferation in many types of cancer. However, the molecular regulation underlying MCM2 in lung cancer cells is poorly understood. In this study, we investigated the role of MCM2 in lung adenocarcinoma A549 (wild-type p53) and H1299 (null p53) cells. MCM2 overexpression increased cell proliferation in A549 cells while silencing MCM2 decreased cell proliferation in H1299 cells. We performed global quantitative phosphoproteomic analysis to uncover the important downstream networks regulated by MCM2 in lung cancer cells. We identified 1484 phosphorylation sites in 593 phosphoproteins of MCM2-overexpressed A549 cells. Of these phosphosites, 110 phosphoproteins were significantly changed in response to MCM2 overexpression. In addition, we identified 1599 phosphorylation sites in 592 phosphoproteins of MCM2-silenced H1299 cells. Of these phosphosites, 57 phosphoproteins were significantly changed in response to MCM2 silencing. The differentially regulated phosphoproteins are involved in biological functions such as RNA splicing, cell cycle and cytoskeleton regulation. Functional study demonstrated that MCM2 overexpression promoted cell migration in A549 cells. Moreover, silencing MCM2 inhibits cell migration and induces cell cycle arrest in H1299 cells. Furthermore, we observed a common phosphorylation change at Ser-99 of high mobility group protein HMG-I/HMG-Y (HMGA1) in both MCM2 overexpression and silencing, indicating an important regulatory effect of Ser-99 HMGA1 on lung cancer cells. The phosphoproteomic profiling of MCM2 in lung cancer cells provides new insight about phosphorylation networks regulated by MCM2 and reveals novel targets for lung cancer therapy.
2018-10-24 | PXD002736 | Pride
Project description:Aspergillus terreus is an emerging fungal pathogen in immunocompromised patients. Due to intrinsic resistance of AmB against A. terreus and acquiring resistance to azoles, alternative antifungal strategy needs investigation. Thus, we explored the activity of phytochemicals such as Shikonin, gallic acid, coumaric acid and quercetin against A. terreus. Amongst these, shikonin showed significant inhibition at MIC50;2 µg/ml, considered for proteome profiling.
2021-06-19 | PXD016797 | Pride
Project description:To investigate the role of shikonin in the development of colon cancer, we treated HCT116 cells with shikonin for 24 hours We then used RNA-seq data from HCT116 cells for gene expression profiling
2024-09-13 | GSE234709 | GEO
Project description:To investigate how the acetylation state of SIRT6 affects its tumor suppressive function in non-small cell lung cancer (NSCLC) cells, we established A549 and H1299 NSCLC cell lines stably expressing either control vector, FLAG-SIRT6 WT, K3R, or K3Q mutants. We then performed gene expression profiling analysis using data obtained from RNA-seq of established A549 and H1299 cells.
2022-08-28 | GSE212057 | GEO
Project description:After over 25cycle and 18month's induction of shikonin, K562 cell show maginal resistance to shikonin but great change in gene expression We use microarray to detect the global gene expression change of shikonin resistant cell
2011-12-10 | GSE34298 | GEO
Project description:Background: Lung cancer, particularly lung adenocarcinoma, remains one of the most lethal malignancies globally. Identifying aberrant molecular pathways and potential therapeutic targets is pivotal for improving patient outcomes. This study focused on the role of GSE1 (genetic suppressor element 1) in lung adenocarcinoma, elucidating its interaction mechanisms and downstream effects. Objectives: 1. Determine the expression levels of GSE1 in lung adenocarcinoma tissues and its implication on cancer cell behaviors. 2. Investigate the effects of GSE1 depletion on the proliferation and migration capabilities of A549 and H1299 lung adenocarcinoma cell lines. 3. Elucidate the potential cellular partners of GSE1, with a particular focus on its interaction with histone deacetylase 1 (HDAC1) and the broader BRAF-HDAC complex (BHC). 4. Analyze the transcriptomic changes following GSE1-knockdown in A549 cells to pinpoint its broad molecular influence. 5. Examine the possible cooperative role of GSE1 and HDAC1 in modulating the expression of significant genes, especially the tumor suppressor gene KLF6. Methods: GSE1 expression was assessed in lung adenocarcinoma tissues and correlated with cell behaviors. The effects of GSE1 depletion were studied in A549 and H1299 cells. Immunoprecipitation assays were utilized to confirm GSE1's interactions. Transcriptomic analysis identified differentially expressed genes post-GSE1-knockdown, with a focus on genes harboring HDAC1 binding sites. The relationship between GSE1 and KLF6 expression was verified using RT-qPCR and western blotting. Results: GSE1 was found to be upregulated in lung adenocarcinoma. Its depletion inhibited proliferation and migration in both A549 and H1299 cells. GSE1 was demonstrated to interact with HDAC1 and other BHC components. Following GSE1-knockdown, 207 genes were upregulated and 159 were downregulated, with 140 genes showcasing HDAC1 binding sites. Among these genes, GSE1 was revealed to inhibit the transcription of the tumor suppressor gene KLF6. Conclusion: GSE1 plays a central role in promoting non-small cell lung cancer progression, potentially through its cooperation with HDAC1. This interaction appears to downregulate KLF6 expression, highlighting a novel molecular pathway that can be targeted for therapeutic interventions in lung adenocarcinoma.
2023-09-10 | GSE242323 | GEO
Project description:After over 25cycle and 18month's induction of shikonin, K562 cell show maginal resistance to shikonin but great change in gene expression We use microarray to detect the global gene expression change of shikonin resistant cell K562 cell was treated by 4uM shikonin for 4hours, then allowed to die and grow back in fresh medium. Once recovered, cells were immidiatly subjected to another treatment.
2011-12-10 | E-GEOD-34298 | biostudies-arrayexpress
Project description:Analysis of H1975, A549 and H1299 cells treated with 12.8 µM Omomyc or vehicle (PBS) for three days.
2019-04-01 | GSE126453 | GEO
Project description:Tumor resistance to radiotherapy is a therapeutic challenge in the treatment of patients with lung cancer. Cyclin-dependent kinase 5 (CDK5) has been proposed to participate in cell proliferation, migration and invasion; drug resistance; and immune evasion. However, the functions and regulatory mechanisms of CDK5 in lung cancer radioresistance have not been investigated.SiRNAs and ShRNAs were used to knock down CDK5 in A549 and H1299 cells. The effects of CDK5 depletion on the tumorigenic behaviors of non-small cell lung cancer (NSCLC) cells were evaluated in vitro and in vivo. Gene expression was examined by RNA-seq and quantitative real-time PCR.
2021-04-30 | GSE148532 | GEO