Epigenetic evaluation of thyme oil anticancer effect in gastric cancer
Project no. 23451 · Status: Kapanmış · 2022
Summary
<p>Gastric cancer (GC) poses a challenge in clinical approach and prognosis due to its heterogeneity in both location and molecular underpinnings. In addition to the genetic makeup of GC, novel epigenetic irregularities with prognostic value continue to be discovered. However, targeting epigenetic modifications contributing to tumor progression by triggering driver epigenetic changes or genetic irregularities initiating GC, particularly with natural compounds instead of systemically applied chemotherapeutics, may result in a treatment process that is both side-effect-free and comfortable for GC patients.</p><p>While Origanum onites L. has demonstrated anticancer effects, including antiproliferative, apoptotic, antiangiogenic, and antimigratory activities, in various cancer types, its potential for epigenetic modification in any cancer type, especially its impact on GC, remains unexplored.</p><p>This study aims to reveal the regulatory activity of Origanum onites L. on promoter-specific histone modifications in AGS cells (an in vitro model for GC) and healthy gastric epithelium GES1 cells. Initially, the activity of the most extensively studied target gene promoters in GC was examined, and modifications were selected for analysis using ChIP-PCR with the EpiQuik Chromatin Immunoprecipitation kit. Validation of these changes in global histone modification was performed using the Histone H3 modification multiplex assay kit. Changes in the expression of modifier enzymes causing epigenetic alterations and genes associated with epigenetic changes in gastric cancer were assessed using real-time qRT-PCR.</p><p>Following OOEO treatment, ChIP-PCR results indicated a contribution to the reorganization of modifications through increased acetylation and decreased methylation of H3K9as and H3K27me3 modifications in the promoter regions of tumor suppressors, and the opposite activity in the promoters of oncogenes. No significant differences were observed in the H3K9me3, H3K4me3, and H3K27As modifications in the promoter regions of the examined genes between control and dose groups. Post-treatment with OOEO revealed differential expression of genes and histone modifier enzymes in promoter regions, supporting alterations in histone modifications.</p><p>OOEO application may alleviate the epigenetic burden of traditional treatment methods for gastric cancer, particularly when used in neoadjuvant or combinatory approaches.</p>