Bibliographic Details
Title: |
Pseudolaric acid B triggers ferritinophagy and ferroptosis via upregulating NCOA4 in lung adenocarcinoma cells. |
Authors: |
Yu’e Miao, Qiao Yin, Lifeng Ping, Huan Sheng, Jin Chang, Wentong Li, Shijun Lv |
Source: |
Journal of Cancer Research & Therapeutics; Dec2023, Vol. 19 Issue 6, p1646-1653, 8p |
Subject Terms: |
APOPTOSIS, LUNGS, ADENOCARCINOMA, IRON, REACTIVE oxygen species, FERRITIN |
Abstract: |
Background: Ferroptosis is a novel subtype of programmed cell death caused by iron-dependent lipid peroxidation and excessive reactive oxygen species (ROS) production. Small-molecule ferroptotic drugs have the probability of selectively targeting the specific features of aggressive tumor cells. In particular, pseudolaric acid B (PAB) triggered ferroptosisin breast cancer cells. The aim of this study is to explore the antitumor effect of PAB on A549 cells and provide a theoretical basis for the further development and clinical application of PAB. Methods: First, relevant databases were used to predict of target genes related to PAB, Then, EdU proliferation assay, colony formation and wound-healing assays were applied to calculate A549 cells proliferative abilities. Measurement of ferrous iron, lipid peroxidation, ROS, malondialdehyde (MDA) and glutathione (GSH) were utilized to explore the relevant mechanism. Results: We showed that PAB decreased the viability of lung adenocarcinoma cells in vitro, which was accompanied by abnormally elevated levels of intracellular ferrous iron and overproduction of lipid reactive oxidate species (L-ROS). In turn, deferoxamine (DFO) significantly rescued PAB-induced lipid peroxidation. PAB also improved the intracellular labile iron pool by promoting ferritin autophagy via the upregulation of the nuclear receptor coactivator 4 (NCOA4). Moreover, silencing of NCOA4 alleviated PAB-inducedferroptotic death and reduced the levels of intracellular ferrous iron. Conclusions: In summary, PAB-triggered ferroptosis in lung adenocarcinoma cells by enhancing ferritinophagy. thus, PAB is a potential therapeutic agent for lung adenocarcinoma. [ABSTRACT FROM AUTHOR] |
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Database: |
Complementary Index |