Shikonin suppresses diffuse large B-cell lymphoma progression by inducing ferritinophagy and ferroptosis via lncRNA ADPGK-AS1 downregulation

  • J Enzyme Inhib Med Chem. 2026 Dec;41(1):2674446. doi: 10.1080/14756366.2026.2674446.
Can Chen  1 ,  Xiaofei Chen  2 ,  Xilian Huang  1 ,  Yaping Xie  1 ,  Pengfei Shi  1 ,  Shenxian Qian  1 ,  Zhenzhen Chen  1
Affiliations
  • 1. Department of Hematology, Affiliated Hangzhou First People's Hospital, School of Medicine, Westlake University, Hangzhou, Zhejiang, China.
  • 2. Zhejiang Chinese Medical University, Hangzhou, Zhejiang, China.
PMID: 42295078 DOI: 10.1080/14756366.2026.2674446
Abstract

Shikonin, a natural compound, exhibits antitumor effects in DLBCL, but its mechanism remains unclear. Shikonin's cytotoxicity in DLBCL cells was assessed by MTT assays. Ferroptosis and lipid peroxidation markers were analysed via flow cytometry and biochemical kits. Mechanisms were explored using gene knockdown/overexpression, dual-luciferase assays, RNA pull-down, proteomics, RIP, FISH, and ChIP. Key proteins and genes involved in ferritinophagy and Ferroptosis were examined by Western blot, RT-qPCR, and immunofluorescence, with findings validated in a nude mouse xenograft model. Shikonin triggers ferritinophagy and Ferroptosis by increasing iron accumulation and lipid peroxidation. LncRNA ADPGK-AS1 protects against Ferroptosis by regulating MT2A via eIF4G1 interaction. Shikonin triggers ferritinophagy and Ferroptosis by disrupting iron metabolism and redox balance. The eIF4G1-ADPGK-AS1/MT2A axis mitigates these effects, revealing shikonin's antitumor mechanism and therapeutic potential.

Keywords
ADPGK-AS1; Diffuse large B-cell lymphoma; ferritinophagy; ferroptosis; shikonin.
Products