Scholarlink

<p>Costunolide (COS) is a bioactive sesquiterpene lactone compound extracted from <i>Aucklandia lappa</i>, known for its anticancer, anti-inflammatory, and antioxidant properties, aligning with the traditional Chinese medicine theory of "clearing heat and dispersing nodules" in the treatment of breast ailments. Network pharmacology identified EGFR as the core target of COS, with enrichment analysis revealing the EGFR/ERK/AKT axis as a key pathway. Molecular docking demonstrated strong binding affinity of COS to the EGFR kinase domain, relying on hydrogen bonds and hydrophobic interactions. In vitro experiments showed that COS inhibited TNBC cell proliferation and induced apoptosis. Mechanistically, COS increased EGFR ubiquitination, leading to a decrease in EGFR protein levels, thereby inhibiting EGFR phosphorylation and the activation of downstream ERK and Akt signaling pathways. EGF could partially reverse the growth inhibitory effects of COS, confirming the critical role of EGFR. This study elucidates that COS exerts its anti-TNBC effects by inducing EGFR ubiquitination and degradation, thereby inhibiting the ERK/AKT signaling pathway. This finding integrates traditional Chinese medicine theory with modern molecular oncology mechanisms, providing a reference for the development of plant-derived multi-target anticancer drugs.</p>

错误：搜索内容不能为空，请输入英文关键词
错误：关键词超出字数限制，请精简
高级检索

Study on the mechanism of costunolide inhibiting triple-negative breast cancer by EGFR ubiquitination and degradation to suppress the ERK/AKT signaling pathway

  • 期刊论文

  • 发表日期：

    2025年11月4日

查看全文
  • Ying Li,
  • Junjie Mu,
  • Qiuxiong Chen,
  • Qian Ming,
  • Chaohong Zhu,
  • Yujie Xiao,
  • Baoli Qiu,
  • Xue Zhang,
  • Baoshun Zhang,
  • Xian Yang

摘要

Costunolide (COS) is a bioactive sesquiterpene lactone compound extracted from Aucklandia lappa, known for its anticancer, anti-inflammatory, and antioxidant properties, aligning with the traditional Chinese medicine theory of "clearing heat and dispersing nodules" in the treatment of breast ailments. Network pharmacology identified EGFR as the core target of COS, with enrichment analysis revealing the EGFR/ERK/AKT axis as a key pathway. Molecular docking demonstrated strong binding affinity of COS to the EGFR kinase domain, relying on hydrogen bonds and hydrophobic interactions. In vitro experiments showed that COS inhibited TNBC cell proliferation and induced apoptosis. Mechanistically, COS increased EGFR ubiquitination, leading to a decrease in EGFR protein levels, thereby inhibiting EGFR phosphorylation and the activation of downstream ERK and Akt signaling pathways. EGF could partially reverse the growth inhibitory effects of COS, confirming the critical role of EGFR. This study elucidates that COS exerts its anti-TNBC effects by inducing EGFR ubiquitination and degradation, thereby inhibiting the ERK/AKT signaling pathway. This finding integrates traditional Chinese medicine theory with modern molecular oncology mechanisms, providing a reference for the development of plant-derived multi-target anticancer drugs.