1. Academic Validation
  2. Neobavaisoflavone induces pyroptosis of liver cancer cells via Tom20 sensing the activated ROS signal

Neobavaisoflavone induces pyroptosis of liver cancer cells via Tom20 sensing the activated ROS signal

  • Phytomedicine. 2023 Jul 25:116:154869. doi: 10.1016/j.phymed.2023.154869.
Yaru Li 1 Renshuang Zhao 1 Zhiru Xiu 2 Xia Yang 1 Yilong Zhu 2 Jicheng Han 3 Shanzhi Li 2 Yue Li 2 Lili Sun 1 Xiao Li 4 Ningyi Jin 5 Yiquan Li 6
Affiliations

Affiliations

  • 1 Medical College, Yanbian University, Yanji, 133002, PR China.
  • 2 Academician Workstation of Jilin Province, Changchun University of Chinese Medicine, Changchun, 130117, PR China.
  • 3 Academician Workstation of Jilin Province, Changchun University of Chinese Medicine, Changchun, 130117, PR China; Changchun Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Changchun, 130122, PR China.
  • 4 Medical College, Yanbian University, Yanji, 133002, PR China; Academician Workstation of Jilin Province, Changchun University of Chinese Medicine, Changchun, 130117, PR China; Changchun Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Changchun, 130122, PR China. Electronic address: [email protected].
  • 5 Medical College, Yanbian University, Yanji, 133002, PR China; Academician Workstation of Jilin Province, Changchun University of Chinese Medicine, Changchun, 130117, PR China; Changchun Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Changchun, 130122, PR China; Jiangsu Co-innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, Yangzhou University, Yangzhou, 225009, PR China. Electronic address: [email protected].
  • 6 Medical College, Yanbian University, Yanji, 133002, PR China; Academician Workstation of Jilin Province, Changchun University of Chinese Medicine, Changchun, 130117, PR China. Electronic address: [email protected].
Abstract

Background: Neobavaisoflavone (NBIF), a natural active ingredient isolated from Psoralea, possesses anti-inflammatory, anti-cancer, and antioxidant properties; however, the anti-tumor mechanism of NBIF has not been thoroughly investigated, and the inhibitory effect and inhibitory pathway of NBIF on liver Cancer are still unknown.

Purpose: Our study aimed to explore the effects of NBIF on hepatocellular carcinoma and its potential mechanisms.

Methods: First, we detected the inhibition of NBIF on HCC cells by the CCK8 assay and then observed the morphological changes of the cells under the microscope. Besides, we analyzed the changes in the Pyroptosis level of NBIF when inhibiting the cells through flow cytometry, immunofluorescence, and a western blot assay. Finally, we used a mouse tumor-bearing model to explore the effects of NBIF in vivo on HCCLM3 cells.

Results: NBIF-treated HCC cells exhibited specific features of Pyroptosis. Analysis of pyroptosis-related protein levels revealed that NBIF primarily induced Pyroptosis in HCC cells via the caspase-3-GSDME signaling pathway. Then, we demonstrated that NBIF impacted the protein expression of Tom20 by producing ROS in HCC cells, hence promoting the recruitment of Bax to mitochondria, activating Caspase-3, cutting GSDME, and triggering Pyroptosis.

Conclusions: By activating ROS, NBIF was able to trigger Pyroptosis in HCC cells, providing an experimental basis for the future study of new treatments for liver Cancer.

Keywords

GSDME; ROS; Tom20; neobavaisoflavone; pyroptosis.

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