Gentian violet induces apoptosis and ferroptosis via modulating p53 and MDM2 in hepatocellular carcinoma.
Year: 2022
Type: article
Abstract: . Both ferroptosis inhibitor Ferrostain-1 (Fer-1) and apoptosis inhibitor Z-VAD-KFM (Z-VAD) partially attenuated GV-induced growth-inhibitory effects, while combined treatment of Fer-1 and Z-VAD completely abolished GV's activities. Increased levels of intracellular reactive oxygen species (ROS) were detected after GV treatment. Interestingly, GV elevated the expression levels of both p53 and its negative regulator MDM2, which was dependent on the expression of the dehydrogenase/reductase protein Hep27. Simultaneously silencing both the MDM2 and p53 genes by siRNAs abolished ROS production and partially rescued the cell death induced by GV treatment. Our data demonstrate a GV-Hep27-MDM2-p53 signaling cascade that regulates ferroptosis and apoptosis. Furthermore, our findings provide insights into understanding the anti-tumor function of GV and present the basis of new therapeutic strategies for the treatment of HCC.
Source: PubMed
Authors: Jingyi Chen, Fangxin Zhao, Hongxin Yang, Jianxun Wen, Ying Tang, Fang Wan, Xuan Zhang, Jianqiang Wu
Language: English
Subfield: Cancer Research
Domain: Life Sciences
Open Access status: green
OpenAlex ID: W4298349753