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

新巴伐利亚异黄酮通过 Tom20 感知激活的 ROS 信号诱导肝癌细胞焦亡

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作者:Yaru Li, Renshuang Zhao, Zhiru Xiu, Xia Yang, Yilong Zhu, Jicheng Han, Shanzhi Li, Yue Li, Lili Sun, Xiao Li, Ningyi Jin, Yiquan Li

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.

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.

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.

Purpose

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

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.

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