2. Academic Validation
  3. Osthole inhibits proliferation and induces autophagy-dependent ferroptosis of cervical cancer cells through induction of TFR1

Osthole inhibits proliferation and induces autophagy-dependent ferroptosis of cervical cancer cells through induction of TFR1

  • Food Chem Toxicol. 2025 Sep:203:115577. doi: 10.1016/j.fct.2025.115577.
Linjun Li 1,  Yue Zhao 1,  Xiaojuan Li 1,  Muzhao Tian 2,  JiaoQing Wei 3,  Wanyu Xie 3,  Caishan Liu 4,  Ping Dai 5,  Juan Wang 6
Affiliations

Affiliations

  • 1 Guangxi Key Laboratory of Drug Discovery and Optimization, School of Pharmacy, Guilin Medical University, Guilin, 541199, China; Department of Pharmacy, Guilin Medical University, 541199, Guilin, China.
  • 2 Guangxi Key Laboratory of Drug Discovery and Optimization, School of Pharmacy, Guilin Medical University, Guilin, 541199, China; Department of Pharmacy, Guilin Medical University, 541199, Guilin, China; Faculty of Basic Medicine, Guilin Medical University, No. 109, 541004, Guilin, China.
  • 3 Department of Pharmacy, Guilin Medical University, 541199, Guilin, China.
  • 4 Department of Pathology, The Second Affiliated Hospital of Guilin Medical University, 541100, China.
  • 5 Guangxi Key Laboratory of Drug Discovery and Optimization, School of Pharmacy, Guilin Medical University, Guilin, 541199, China; Department of Pharmacy, Guilin Medical University, 541199, Guilin, China. Electronic address: 59449273@qq.com.
  • 6 Guangxi Key Laboratory of Drug Discovery and Optimization, School of Pharmacy, Guilin Medical University, Guilin, 541199, China; Department of Pharmacy, Guilin Medical University, 541199, Guilin, China; Faculty of Basic Medicine, Guilin Medical University, No. 109, 541004, Guilin, China; Guangxi Key Laboratory of Molecular Medicine in Liver Injury and Repair, The Affiliated Hospital of Guilin Medical University, Guilin, 541001, China; Guangxi Health Commission Key Laboratory of Basic Research in Sphingolipid Metabolism Related Diseases, The Affiliated Hospital of Guilin Medical University, Guilin, 541001, China. Electronic address: juanlovelife@163.com.
PMID: 40446951 DOI: 10.1016/j.fct.2025.115577
Abstract

Osthole (OST), a natural coumarin, exerts its Anticancer effects by inducing Cancer cell Necroptosis, Apoptosis, Pyroptosis or Autophagy. In He La cells, OST cause mitochondrial atrophy, increased membrane density and reduced cristae, which are characteristics of Ferroptosis. However, the mechanisms of OST-induced Ferroptosis in cervical Cancer cells remain unclear. In the present study, we found that OST inhibited He La cells' proliferation which triggered Ferroptosis. Further studies showed that Ferroptosis or Autophagy inhibition could reverse the inhibitory effects of OST on He La cell proliferation, and significantly inhibited Ferroptosis and Autophagy induced by OST. Moreover, Autophagy stimulation enhanced the Ferroptosis induction of OST, while Ferroptosis induction in turn enhanced the Autophagy levels caused by OST. Furthermore, Transferrin Receptor 1 (TRF-1) silencing effectively reduced OST-induced Ferroptosis and Autophagy, while TFR1 overexpression notably enhanced OST-induced Ferroptosis and Autophagy in He La cells. In addition, animal experiments demonstrated that overexpression of TFR1 effectively suppressed tumor growth in cervical Cancer He La cells, and its expression was associated with the activation of Ferroptosis and Autophagy. In conclusion, our study revealed the detailed mechanism of OST-induced He La cells Ferroptosis and Autophagy, and the association between Autophagy and Ferroptosis in OST-induced cell death.

Keywords

Autophagy; Cervical cancer; Ferroptosis; Osthole; TFR1.

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