ArticlePLoS neglected tropical diseases2018
Inhibition of histone methyltransferase EZH2 in Schistosoma mansoni in vitro by GSK343 reduces egg laying and decreases the expression of genes implicated in DNA replication and noncoding RNA metabolism.
Article in PLoS neglected tropical diseases, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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14 citing papers in PubMed, 30 citations in OpenAlex.
- Long Non-Coding RNAs Identified as Hub Genes by Weighted Gene Co-Expression Network Analysis inInternational journal of molecular sciences · 2026Article
- Long non-coding RNAs are essential for Schistosoma mansoni pairing-dependent adult worm homeostasis and fertility.PLoS pathogens · 2023Article
- Chemical modulation ofWellcome open research · 2023Article
- RUNX3/H3K27me3 Co-Expression Defines a Better Prognosis in Surgically Resected Stage I and Postoperative Chemotherapy-Naive Non-Small-Cell Lung Cancer.Journal of oncology · 2022Article
- Assessment of reference genes at six different developmental stages of Schistosoma mansoni for quantitative RT-PCR.Scientific reports · 2021Article
- Epigenetic Markers Associated with Schistosomiasis.Helminthologia · 2021Article
- Long non-coding RNA levels can be modulated by 5-azacytidine in Schistosoma mansoni.Scientific reports · 2020Article
- Pharmacological inhibition of lysine-specific demethylase 1 (LSD1) induces global transcriptional deregulation and ultrastructural alterations that impair viability in Schistosoma mansoni.PLoS neglected tropical diseases · 2020Article
- Inhibition of 19S proteasome deubiquitinating activity in Schistosoma mansoni affects viability, oviposition, and structural changes.Parasitology research · 2020Article
- The antischistosomal potential of GSK-J4, an H3K27 demethylase inhibitor: insights from molecular modeling, transcriptomics and in vitro assays.Parasites & vectors · 2020Article
- Identification of 6-(piperazin-1-yl)-1,3,5-triazine as a chemical scaffold with broad anti-schistosomal activities.Wellcome open research · 2020Article
- The repositioning of epigenetic probes/inhibitors identifies new anti-schistosomal lead compounds and chemotherapeutic targets.PLoS neglected tropical diseases · 2019Article
- In vitro activity of aryl-thiazole derivatives against Schistosoma mansoni schistosomula and adult worms.PloS one · 2019Article
- Effects of the Environment on Developmental Plasticity and Infection Success ofFrontiers in microbiology · 2019Review
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Authors and funding
14 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundThe possibility of emergence of praziquantel-resistant Schistosoma parasites and the lack of other effective drugs demand the discovery of new schistosomicidal agents. In this context the study of compounds that target histone-modifying enzymes is extremely promising. Our aim was to investigate the effect of inhibition of EZH2, a histone methyltransferase that is involved in chromatin remodeling processes and gene expression control; we tested different developmental forms of Schistosoma mansoni using GKS343, a selective inhibitor of EZH2 in human cells. METHODOLOGY/PRINCIPAL
findingsAdult male and female worms and schistosomula were treated with different concentrations of GSK343 for up to two days in vitro. Western blotting showed a decrease in the H3K27me3 histone mark in all three developmental forms. Motility, mortality, pairing and egg laying were employed as schistosomicidal parameters for adult worms. Schistosomula viability was evaluated with propidium iodide staining and ATP quantification. Adult worms showed decreased motility when exposed to GSK343. Also, an approximate 40% reduction of egg laying by GSK343-treated females was observed when compared with controls (0.1% DMSO). Scanning electron microscopy showed the formation of bulges and bubbles throughout the dorsal region of GSK343-treated adult worms. In schistosomula the body was extremely contracted with the presence of numerous folds, and growth was markedly slowed. RNA-seq was applied to identify the metabolic pathways affected by GSK343 sublethal doses. GSK343-treated adult worms showed significantly altered expression of genes related to transmembrane transport, cellular homeostasis and egg development. In females, genes related to DNA replication and noncoding RNA metabolism processes were downregulated. Schistosomula showed altered expression of genes related to cell adhesion and membrane synthesis pathways. CONCLUSIONS/SIGNIFICANCE: The results indicated that GSK343 presents in vitro activities against S. mansoni, and the characterization of EZH2 as a new potential molecular target establishes EZH2 inhibitors as part of a promising new group of compounds that could be used for the development of schistosomicidal agents.
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