Gene expression of colorectal cancer cells treated with Celastrol or compound 19-048
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA816185 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR18328100_1.fastq.gz | Fastqsanger.gz | |||
| SRR18328100_2.fastq.gz | Fastqsanger.gz | |||
| SRR18328101_1.fastq.gz | Fastqsanger.gz | |||
| SRR18328101_2.fastq.gz | Fastqsanger.gz | |||
| SRR18328102_1.fastq.gz | Fastqsanger.gz |
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Project description:As a terpenoids natural product isolated from the plant Thunder God Vine, Celastrol is widely studied for its pharmacological activities, including anti-tumor activities. However, the clinical application of Celastrol is strictly limited due to its severe side effects. Without identification and validation of the target protein of Celastrol, it is difficult to determine whether its anti-tumor activities and side effects are due to inhibition of the same protein. Using a new computational tool we have developed for target discovery, peroxiredoxin I (PRDX1) was identified as the ROS-manipulating target protein of Celastrol. High-resolution crystal structure revealed the unique binding mode of Celastrol with PRDX1, via covalent reaction to the catalytic Cys-173 residue of PRDX1. New derivative compound named 19-048 with improved potency against PRDX1 and selectivity towards PRDX2~PRDX6 were synthesized. Both Celastrol and compound 19-048 effectively suppressed the proliferation of colorectal cancer cells. While these anti-tumor efficacy was significantly diminished on xenograft nude mice bearing PRDX1 knock-down colorectal cancer cells. Several downstream genes of p53 were dramatically up-regulated in the presence of Celastrol and compound 19-048. Our findings reveal that the side effects of Celastrol could be reduced via structural modification, and PRDX1 inhibition is promising for the treatment of colorectal cancer.
2022-12-31 | GSE198630 | GEO
Project description:Purpose: This study aimed to explore the mechanism of Celastrol in improving psoriasis through single-cell transcriptomics Methods: Supplementation with intragastric administration of celastrol in C57BL/6 mice to observe its effect on IMQ-induced psoriasis. Single-cell RNA sequencing were performed to explore the role of celastrol for IMQ-induced psoriasis. Results: A natural product library was used to screen for a small molecule compound, celastrol, that could interfere with fibroblast-macrophage communication. It was demonstrated that celastrol targeted low-denisity lipoprotein receptor-related protein 1 (LRP1) to inhibit fibroblast secretion of CCL2 and inhibited psoriasis progression by reducing its recruitment to macrophages, thereby blocking communication between the two cells Conclusion: We report that celastrol targeted low-denisity lipoprotein receptor-related protein 1 (LRP1) to inhibit fibroblast secretion of CCL2 and inhibited psoriasis progression by reducing its recruitment to macrophages. The use of celastrol maybe a noveltherapeuticoption for psoriasis.
2024-04-20 | GSE231728 | GEO
Project description:Stress response pathways allow cells to rapidly sense and respond to deleterious environmental changes, including those caused by pathophysiological disease states. A previous screen for small molecules capable of activating the human heat shock response identified the triterpenoid celastrol as a potent activator of the heat shock transcription factor HSF1. We show here that celastrol likewise activates the homologous Hsf1 of Saccharomyces cerevisiae. Celastrol induced Hsf1 hyperphosphorylation and concurrently activated a synthetic transcriptional reporter as well as endogenous inducible Hsp70 proteins at the same effective concentration seen in mammalian cells. Moreover, celastrol treatment conferred significant resistance to subsequent lethal heat shock. Transcriptional profiling experiments revealed that in addition to Hsf1, celastrol treatment induced the Yap1-dependent oxidant defense regulon. Oxidative stress-responsive genes were likewise induced in mammalian cells, demonstrating that celastrol simultaneously activates two major cellular stress-mediating pathways. As the induction of cellular stress pathways has implications in the treatment of a variety of human diseases including neurodegenerative diosorders, cardiovascular disease and cancer, celastrol thus represents an attractive therapeutic compound. Keywords: single-dose, single time-point gene induction by natural small molecule celastrol compared to heat shock in wild type (BY4741) Saccahromyces cerevisiae
2006-08-26 | GSE5608 | GEO
Project description:Most studies of responses to transcriptional stimuli measure changes in cellular mRNA concentrations. By sequencing nascent RNA instead, it is possible to detect changes in transcription in minutes rather than hours, and thereby distinguish primary from secondary responses to regulatory signals. Here, we describe the use of PRO-seq to characterize the immediate transcriptional response in human cells to celastrol, a compound derived from traditional Chinese medicine that has potent anti-inflammatory, tumor-inhibitory and obesity-controlling effects. Our analysis of PRO-seq data for K562 cells reveals dramatic transcriptional effects soon after celastrol treatment at a broad collection of both coding and noncoding transcription units. This transcriptional response occurred in two major waves, one within 10 minutes, and a second 40-60 minutes after treatment. Transcriptional activity was generally repressed by celastrol, but one distinct group of genes, enriched for roles in the heat shock response, displayed strong activation. Using a regression approach, we identified key transcription factors that appear to drive these transcriptional responses, including members of the E2F and RFX families. We also found sequence-based evidence that particular TFs drive the activation of enhancers. We observed increased polymerase pausing at both genes and enhancers, suggesting that pause release may be widely inhibited during the celastrol response. Our study demonstrates that a careful analysis of PRO-seq time course data can disentangle key aspects of a complex transcriptional response, and it provides new insights into the activity of a powerful pharmacological agent.
2017-03-22 | GSE96869 | GEO
Project description:Purpose: The goals of this study was to (1) evaluate the protective effect of celastrol on alpha-naphthylisothiocyanate (ANIT)-induced cholestasis and (2) which genes were recovered by celastrol. Methods:To investigate the protective effect of celastrol on ANIT-induced cholestasis, the WT mice were randomly assigned into two groups, respectively (n=3): (1) ANIT; (2) ANIT+Celastrol. ANIT+Celastrol group was orally treated with celastrol (10 mg/kg dissolved in 1% DMSO + 2% Tween 80 + 97% water) for 5 consecutive days. After celastrol was treated for 3 days, ANIT and ANIT+Celastrol groups were given a single oral dose of ANIT. All mice were killed 48 h after ANIT administration. Liver samples were harvested and frozen at -80 °C before analysis. Results: A total of 978 DEGs were identified. Large numbers of these DEGs were related to activation of SIRT1, which included increased FXR signaling and inhibition of PPARγ, nuclear factor-kappa B (NF-κB), and P53 signaling. Conclusions: Celastrol could protect ANIT-induced cholestasis by recovering disrupted Sirt1 level.
2018-02-09 | GSE110391 | GEO
Project description:Celastrol is a natural product that affects LNCaP gene expression by 6h; We used microarrays to detail the global programme of gene expression affected by celastrol treatment at 6h Experiment Overall Design: LNCaP cells were grown to 50% confluency and treated with celastrol for 6h prior to direct Trizol lysis and RNA isolation
2008-11-07 | E-GEOD-5505 | biostudies-arrayexpress
Project description:Celastrol has been shown to sensitize leptin receptor signaling and reduce ER stress. Current microarray data provide the gene expression profile in mouse embryonic fibroblasts (MEFs) after Celastrol treatment compared with control.
2016-07-08 | GSE84154 | GEO
Project description:In the present study, we analyzed single-cell multi-omics data from psoriasis patients and healthy individuals and found that more fibroblast-macrophage communication was present in the dermis of psoriasis lesions, exacerbating psoriasis progression. A natural product library was used to screen for a small molecule compound, celastrol, that could interfere with fibroblast-macrophage communication. It was demonstrated that celastrol targeted low-denisity lipoprotein receptor-related protein 1 (LRP1) to inhibit fibroblast secretion of CCL2 and inhibited psoriasis progression by reducing its recruitment to macrophages, thereby blocking communication between the two cells. Moreover, conditional knockdown of LRP1 by fibroblasts significantly improved psoriasis in mice, suggesting that LRP1 may be an important target for the treatment of psoriasis.
2024-03-31 | GSE230842 | GEO
Project description:Given that celastrol?s leptin-sensitizing effect requires high levels of circulating leptin, but lean mice have low levels of circulating leptin so that celastrol has no effect on lean mice. Analysis celastrol-induced hypothalamic gene expression profile change in lean mice will also be serving as negative control for DIO mice analysis.
2018-12-27 | GSE124356 | GEO
Project description:Celastrol is a natural product that affects LNCaP gene expression by 6h We used microarrays to detail the global programme of gene expression affected by celastrol treatment at 6h Keywords: drug treatment
2006-09-01 | GSE5505 | GEO