2. Academic Validation
  3. Decursin induces ferroptosis via the NRF2/GPX4/SLC11A2 axis and suppresses migration in hepatocellular carcinoma

Decursin induces ferroptosis via the NRF2/GPX4/SLC11A2 axis and suppresses migration in hepatocellular carcinoma

  • Biomed Pharmacother. 2026 Feb:195:118941. doi: 10.1016/j.biopha.2025.118941.
Jingwei Li 1,  Zhaoyang Wang 1,  Kaili Wei 1,  Qingqing Liu 1,  Lu Liang 2,  Jianping Lin 3
Affiliations

Affiliations

  • 1 State Key Laboratory of Medicinal Chemical Biology, College of Pharmacy and Tianjin Key Laboratory of Molecular Drug Research, Nankai University, Haihe Education Park, 38 Tongyan Road, Tianjin 300353, China.
  • 2 Tianjin BioAI-global Technology Co., Ltd., Tianjin 300140, China.
  • 3 State Key Laboratory of Medicinal Chemical Biology, College of Pharmacy and Tianjin Key Laboratory of Molecular Drug Research, Nankai University, Haihe Education Park, 38 Tongyan Road, Tianjin 300353, China. Electronic address: [email protected].
PMID: 41496356 DOI: 10.1016/j.biopha.2025.118941
Abstract

Hepatocellular carcinoma (HCC) is a leading cause of cancer-related mortality, and durable therapeutic options remain limited. Ferroptosis has emerged as a therapeutically exploitable vulnerability in HCC. Here, we characterized the Anticancer activity of decursin, a natural coumarin derived from Angelica gigas. Decursin reduced the viability and long-term proliferative capacity of HepG2 and Huh7 cells in a dose-dependent manner, with half-maximal inhibitory concentration (IC50) values of approximately 100 μM and 150 μM, respectively. It also impaired migratory and invasive behaviors while inducing oxidative stress, including lipid peroxidation and glutathione depletion, which are hallmarks of Ferroptosis. Integrated transcriptomic and metabolomic profiling revealed a broad disruption of redox and glutathione metabolism, converging on the attenuation of the NRF2-GPX4 antioxidant axis. Computational target prediction and docking further suggested that decursin may influence iron-handling pathways involving SLC11A2, although this relationship requires further validation. In vivo, decursin significantly inhibited tumor growth in xenograft models and reduced NRF2/GPX4 expression. Notably, decursin retained its efficacy in sorafenib-resistant HCC cells. Collectively, these findings identify decursin as a ferroptosis-inducing agent with therapeutic potential in HCC.

Keywords

Decursin; Ferroptosis; GPX4; Hepatocellular carcinoma; NRF2; Sorafenib resistance.

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