Integrated network pharmacology and transcriptomic approach reveal the role of equol in reducing colorectal cancer via regulating multiple cell cycle genes in HCT116 cells

Equol is an isoflavone-derived metabolite known to exhibit strong estrogenic and antioxidant activities. The aim of this paper is twofold: first, to confirm the anticancer potential of equol against colorectal cancer, and second, to reveal the underlying mechanisms. After treatment with 40 μg/mL equol, cell proliferation, cell migration, and colony formation of HCT116 colon cancer cells were inhibited. Network pharmacology and transcriptomics analysis revealed the downregulation of genes related to DNA replication (CCND1, E2F1, CDC6, CDC45, MCM4), leading to G1/S cell cycle arrest and the induction of cell apoptosis, which was confirmed by flow cytometry. Genes associated with the G2-to-M transition (CDK1, CCNA2, CCNB1) were also downregulated. In addition, equol downregulated genes (FOXM1 and ASPM) that control cell migration and invasion. Our data indicate that equol can inhibit colorectal cancer by targeting multiple pathways, suggesting its potential as a key component in the adjuvant treatment of colorectal cancer. [Display omitted] •Equol inhibited colorectal cancer cell proliferation, migration, colony formation.•Network analysis revealed equol's cell cycle regulatory network interactions.•Equol induced G1/S arrest by downregulating CCND1, E2F1, CDC6, CDC45, MCM4.•Equol blocked G2/M transition by downregulating CDK1, CCNA2, CCNB1.