Integrated Transcriptomic and Functional Analysis Reveals Selective Cytotoxicity and Oncogene Suppression Induced by Cinnamon Essential Oil in Cervical Cancer Cells

This study aimed to evaluate the effect of cinnamon (Cinnamomum zeylanicum) essential oil (CEO) on cervical cancer cell lines (HeLa and SiHa) and an immortalized human keratinocyte cell line (HaCaT) by analyzing its impact on gene expression modulation. Total RNA sequencing was performed using the Illumina NovaSeq 6000 platform by Novogene Bioinformatics Technology Co., Ltd. (Beijing, China), with four independent replicates for each cell model. Bioinformatics analysis was conducted using R (v4.3.1), RStudio (v2023.09.1+494), and the open-source Galaxy platform (https://usegalaxy.org; accessed on February 5, 2025). Quality control was performed with FastQC (v0.74+galaxy0). Subsequently, reads were processed with the Rsubread package (v2.14.2), trimmed, and aligned to the human reference genome (GRCh38.p14 v46). The resulting BAM files were used for read counting with FeatureCounts (v2.0.3). Differential expression analysis was carried out using the DESeq2 package for R (v1.42.0). Normalization of gene expression was performed using DESeq2’s median-of-ratios method (median ratio of gene counts relative to the geometric mean per gene). Genes with an adjusted p-value ≤ 0.05 and |Log2FC| ≥ 2 were considered differentially expressed genes (DEGs). Transcriptomic analysis revealed significant upregulation of genes involved in cellular stress responses, DNA damage repair, and protein synthesis. DEGs were enriched in apoptosis, cell cycle regulation, and p53 signaling pathways. Additionally, CEO treatment led to suppression of genes associated with oxidative phosphorylation and cell cycle progression, with HeLa cells showing the highest sensitivity.