Mao Kemin, Wang Xianghong, Hou Yakun, He Xiaowei, Geng Shuo, Sadiq Faizan Ahmed, Lian Yunhe, Sang Yaxin
Department of Food Science and Technology, Hebei Agricultural University, Baoding, Hebei, China.
Advanced Therapies Group, School of Dentistry, College of Biomedical and Life Sciences, Cardiff University, Cardiff CF14 4XY, United Kingdom.
Int J Biol Macromol. 2024 Dec;282(Pt 2):136832. doi: 10.1016/j.ijbiomac.2024.136832. Epub 2024 Oct 24.
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.
雌马酚是一种异黄酮衍生的代谢产物，已知具有强大的雌激素活性和抗氧化活性。本文的目的有两个：第一，确认雌马酚对结直肠癌的抗癌潜力；第二，揭示其潜在机制。用40μg/mL雌马酚处理后，HCT116结肠癌细胞的细胞增殖、细胞迁移和集落形成受到抑制。网络药理学和转录组学分析显示，与DNA复制相关的基因（CCND1、E2F1、CDC6、CDC45、MCM4）下调，导致G1/S期细胞周期阻滞并诱导细胞凋亡，这通过流式细胞术得到证实。与G2期到M期转换相关的基因（CDK1、CCNA2、CCNB1）也下调。此外，雌马酚下调了控制细胞迁移和侵袭的基因（FOXM1和ASPM）。我们的数据表明，雌马酚可通过靶向多种途径抑制结直肠癌，提示其作为结直肠癌辅助治疗关键成分的潜力。
