In Silico Network Toxicology, Molecular Docking, and Multi-Level Bioinformatics Reveal Methyl Eugenol-Induced Hepatocellular Carcinoma Mechanisms in Humans

Karakuş F., Tanrıverdi Z., Kuzu B.

Cancer Medicine, cilt.14, sa.10, 2025 (SCI-Expanded) identifier identifier

  • Yayın Türü: Makale / Tam Makale
  • Cilt numarası: 14 Sayı: 10
  • Basım Tarihi: 2025
  • Doi Numarası: 10.1002/cam4.70768
  • Dergi Adı: Cancer Medicine
  • Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus, Academic Search Premier, BIOSIS, CAB Abstracts, EMBASE, MEDLINE, Veterinary Science Database, Directory of Open Access Journals
  • Anahtar Kelimeler: CCNB1, cell cycle, hepatocellular carcinoma, in silico, methyl eugenol
  • Van Yüzüncü Yıl Üniversitesi Adresli: Evet

Özet

Background: Methyl eugenol (ME), a natural compound found in various essential oils, has recently been classified as a Group 2A carcinogen by the International Agency for Research on Cancer. Methods: This study aims to investigate the potential molecular mechanisms and underlying ME-induced hepatocellular carcinoma (HCC) in humans using network toxicology, molecular docking, and integrative bioinformatics approaches, including transcriptomic and survival analyses of human HCC datasets. Results: Enrichment analysis highlighted significant associations with pathways related to steroid metabolic processes, extracellular exosomes, and diverse binding activities. KEGG pathway enrichment further implicated metabolic pathways in ME-induced HCC development. Integration of STRING and Cytoscape analyses identified 14 hub targets, including key proteins such as AURKB, CCNB1, CDK1, and PLK1. Molecular docking studies demonstrated weak binding affinities of ME to these targets compared to their specific inhibitors. However, microarray data and survival analyses of human HCC samples revealed that AURKB, CCNB1, CDK1, and PLK1 are upregulated in HCC, with higher expression levels correlating with poorer overall survival, particularly for CCNB1. Conclusions: These findings suggest that ME exposure may enhance the expression of these genes in hepatocytes, disrupting the cell cycle and promoting proliferation. This study provides valuable insights into the molecular mechanisms of ME-induced HCC in humans and highlights potential therapeutic targets, such as CCNB1, for further investigation.