2. Academic Validation
  3. Celastrol Induces Ferroptosis by Regulating CERKL to Exert Anti-Gastric Cancer Effect

Celastrol Induces Ferroptosis by Regulating CERKL to Exert Anti-Gastric Cancer Effect

  • Am J Chin Med. 2025;53(3):931-949. doi: 10.1142/S0192415X25500351.
Chang Yang 1 2 3 4,  Rui Xue 1 2 3 4,  Chuling Qin 1 2 3 4,  Lingyue Huang 1 2 3 4,  Rongrong Nie 5,  Yuqin Luo 1 2 3 4,  Siyuan Xu 1 2 3 4,  Ke Tang 1 2 3 4,  Jianning Chen 1 2 3 4,  Lulu Jia 1 2 3 4,  Qinyou Tan 1 2 3 4 6
Affiliations

Affiliations

  • 1 Department of Clinical Pharmacy, School of Pharmacy, Guilin Medical University, Guilin 541001, Guangxi, China.
  • 2 Clinical Pharmacy & Pharmacology Research Institute, Affiliated Hospital of Guilin Medical University, Guilin 541001, Guangxi, China.
  • 3 Guangxi Key Laboratory of Molecular Medicine in Liver Injury and Repair, Affiliated Hospital of Guilin Medical University, Guilin 541001, Guangxi, China.
  • 4 Guangxi Health Commission Key Laboratory of Basic Research in Sphingolipid Metabolism Related Diseases, Affiliated Hospital of Guilin Medical University, Guilin 541001, Guangxi, China.
  • 5 Rehabilitation Department, Affiliated Hospital of Guilin Medical University, Guilin 541001, Guangxi, China.
  • 6 China-USA Lipids in Health and Disease Research Center, Guilin Medical University, Guilin 541001, Guangxi, China.
PMID: 40374372 DOI: 10.1142/S0192415X25500351
Abstract

Gastric Cancer is a significant global health issue. Celastrol, a natural compound, has shown antitumor potential, but its molecular mechanism in gastric Cancer remains unclear. In this study, we treated HGC-27 cells with celastrol and employed CCK8, colony formation, and Transwell assays, revealing its inhibitory effect on cell proliferation and migration. Flow cytometry assay results showed that celastrol could elevate the level of Reactive Oxygen Species (ROS) in HGC-27 cells. By using the iron ion and malondialdehyde (MDA) detection kits, it was found that celastrol promoted the accumulation of iron ions (Fe[Formula: see text] in HGC-27 cells, increased the MDA content, and simultaneously decreased the glutathione (GSH) content. Additionally, Western blot analysis indicated that celastrol exerts an inhibitory effect on the expression of ferroptosis-marker proteins GPX4 and SLC7A11. PCR array and further experiments identified CERKL as a key factor, whose downregulation by celastrol was associated with enhanced Ferroptosis. In vivo, celastrol inhibited tumor growth without affecting body weight or organ histology. Our findings suggest that celastrol may inhibit gastric Cancer via CERKL-regulated Ferroptosis, providing a potential therapeutic strategy.

Keywords

CERKL; Celastrol; Ferroptosis; Gastric Cancer; PCR Array.

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