期刊
INTERNATIONAL JOURNAL OF MEDICAL SCIENCES
卷 18, 期 8, 页码 1899-1909出版社
IVYSPRING INT PUBL
DOI: 10.7150/ijms.54860
关键词
ammonium ferric citrate; non-small-cell lung carcinoma; autophagy; ferroptosis
资金
- National Natural Science Foundation of China [81973899]
- shanghai training project for leading talents of traditional Chinese medicine [ZY(2018-2020)-RCPY-1024]
The study demonstrated that ammonium ferric citrate (AFC) can effectively inhibit the proliferation and invasion of lung cancer cells, induce oxidative stress injury, and ferroptosis. AFC exerts its effects by regulating the expression of cell growth factors, negative regulators of ferroptosis, and autophagy regulators.
The morbidity and mortality rates associated with non-small-cell lung carcinoma (NSCLC) are increasing every year, placing new demands on existing therapies and drugs. Ammonium ferric citrate (AFC) is often used as a food additive for iron supplementation; however, to our knowledge, no studies have investigated whether AFC can induce ferroptosis in NSCLC. In this study, we demonstrated that specific concentrations of AFC effectively inhibit the proliferation and invasion of lung cancer cell lines in vitro using a cell proliferation inhibition test, a transwell assay, and flow cytometry analysis of cell cycle and apoptosis. In addition, AFC significantly induced oxidative stress injury in lung cancer cell lines. A quantitative polymerase chain reaction assay showed that AFC markedly reduced the expression levels of cell growth factors, negative regulators of ferroptosis, and autophagy regulators. Lastly, a protein-protein interaction analysis revealed that glutathione peroxidase 4 (GPX4) exerted its biological role through the regulation of the GSS/GSR complex and downstream GGT family proteins. When the expression of GPX4 changes, its biological activities, such as the glutathione metabolic process, cellular biosynthetic process, cellular response to chemical stimulus, and antioxidant activity, change accordingly, thereby affecting the survival quality and physiological and biochemical activities of cells. Overall, this study verifies that AFC has the biological activity of activating oxidative stress injury in NSCLC cell lines, leading to a decrease in their autophagy and inducing ferroptosis. We also confirmed that the GPX4-GSS/GSR-GGT axis is a crucial target of AFC-induced ferroptosis.
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