2. Academic Validation
  3. Psoralidin induces pyroptosis in both tumor cells and macrophages as well as enhances nature killer cell cytotoxicity to suppress hepatocellular carcinoma

Psoralidin induces pyroptosis in both tumor cells and macrophages as well as enhances nature killer cell cytotoxicity to suppress hepatocellular carcinoma

  • Mol Immunol. 2025 Aug:184:22-31. doi: 10.1016/j.molimm.2025.05.020.
Xianling Wang 1,  Yongjian Xie 2,  Huijie Yang 3,  Chengxian Li 3,  Xinru Wen 3,  Simin Chen 3,  Qing Yao 3,  Congyang Zheng 3,  Chengwei Li 3,  Caiping He 3,  Mingxia Fang 4,  Ce Shi 4,  Ang Huang 5,  Ping Zhang 6,  Zhaofang Bai 7,  Xiaoyan Zhan 8,  Xiaohe Xiao 9
Affiliations

Affiliations

  • 1 Guizhou University of Traditional Chinese Medicine, Guiyang 550025, China; Senior Department of Hepatology, The Fifth Medical Center of PLA General Hospital, Beijing 100039, China; Military Institute of Chinese Materia, the Fifth Medical Centre, General Hospital of PLA, Beijing 100039, China.
  • 2 Guizhou University of Traditional Chinese Medicine, Guiyang 550025, China.
  • 3 Senior Department of Hepatology, The Fifth Medical Center of PLA General Hospital, Beijing 100039, China; Military Institute of Chinese Materia, the Fifth Medical Centre, General Hospital of PLA, Beijing 100039, China.
  • 4 Senior Department of Hepatology, The Fifth Medical Center of PLA General Hospital, Beijing 100039, China; Military Institute of Chinese Materia, the Fifth Medical Centre, General Hospital of PLA, Beijing 100039, China; National Key Laboratory of Kidney Diseases, Beijing 100039, China.
  • 5 The First Medical Center of PLA General Hospital, Beijing 100039, China.
  • 6 Department of Pharmacy, Medical Supplies Center of PLA General Hospital, Beijing 100853, China.
  • 7 Senior Department of Hepatology, The Fifth Medical Center of PLA General Hospital, Beijing 100039, China; Military Institute of Chinese Materia, the Fifth Medical Centre, General Hospital of PLA, Beijing 100039, China; National Key Laboratory of Kidney Diseases, Beijing 100039, China. Electronic address: baizf2008@hotmail.com.
  • 8 Senior Department of Hepatology, The Fifth Medical Center of PLA General Hospital, Beijing 100039, China; Military Institute of Chinese Materia, the Fifth Medical Centre, General Hospital of PLA, Beijing 100039, China; National Key Laboratory of Kidney Diseases, Beijing 100039, China; State Key Laboratory for Quality Ensurance and Sustainable Use of Dao-di Herbs, Beijing, China. Electronic address: xyzhan123@163.com.
  • 9 Guizhou University of Traditional Chinese Medicine, Guiyang 550025, China; Senior Department of Hepatology, The Fifth Medical Center of PLA General Hospital, Beijing 100039, China; Military Institute of Chinese Materia, the Fifth Medical Centre, General Hospital of PLA, Beijing 100039, China; National Key Laboratory of Kidney Diseases, Beijing 100039, China. Electronic address: pharmacy_302@126.com.
PMID: 40479862 DOI: 10.1016/j.molimm.2025.05.020
Abstract

Psoralidin is a major component of the traditional Chinese medicine Psoraleae Fructus, which is derived from the dried mature fruit of the leguminous plant Psoralea corylifolia L. and possesses many pharmacological effects, including anti-tumor effects. However, the mechanism through which psoralidin protects against hepatocellular carcinoma (HCC) remains unclear. In our study, we found that psoralidin induced Pyroptosis and gasdermin E (GSDME) cleavage in HepG2 and Hepa1-6 cells, which were reversed by the Caspase-3 inhibitor Z-DEVD-FMK. Moreover, psoralidin induced mitochondrial Reactive Oxygen Species (ROS) production, leading to Caspase-3 activation and subsequent GSDME cleavage. Interestingly, psoralidin induced Pyroptosis in macrophages via ROS-NLRP3 inflammasome-gasdermin D (GSDMD), leading to the secretion of interleukin (IL)-1β and IL-18, which promoted natural killer (NK) cell activation and its anti-tumor capability. In a mouse model, psoralidin suppressed HCC growth, induced tumor cell Pyroptosis, and enhanced tumor infiltration of T and NK cells. Collectively, our data demonstrate that psoralidin induces Pyroptosis in tumor cells via ROS/Caspase-3/GSDME and triggers Pyroptosis in macrophages via ROS/NLRP3 inflammasome/GSDMD, enhancing NK cell anti-tumor ability, suggesting that psoralidin could be used as a potential therapeutic candidate for HCC.

Keywords

Co-culture; HCC; Psoralidin; Pyroptosis; ROS.

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