Iron-dependent ferroptosis is a form of cell death dependent on iron levels. Cells that undergo ferroptosis have glutathione (GSH) deficiency, reduced Glutathione peroxidase-4 (GPX4) activity and intracellular lipid peroxidation, Mitochondria, lysosomes and many signal pathways are involved in the regulation of ferroptosis. More importantly, many tumor cells resistant to other cell death methods exhibit sensitivity to ferroptosis. Moreover, over recent years, a number of ferroptosis-induced drugs have been recommended for the treatment of malignant tumors. Therefore, the study of ferroptosis is of great significance for future cancer treatments. In this review, we discussed the metabolic process of ferroptosis, the role of different organelles, the typical signaling pathways involved in ferroptosis, as well as natural and synthetic compounds that can induce ferroptosis, aiming to point out new conceptual avenues for utilizing ferroptosis in future cancer treatments.

Glucocorticoids (GC) are widely used to counter the adverse events during cancer therapy; nonetheless, previous studies pointed out that GC may reduce the efficacy of chemotherapy on cancer cells, especially in epidermal growth factor receptor (EGFR)-targeted therapy of head and neck squamous cell carcinoma (HNSCC) remaining to be elucidated. The primary aim of the present study was to probe into the GC-induced resistance of EGFR-targeted drug afatinib and the underlying mechanism. HNSCC cell lines (HSC-3, SCC-25, SCC-9, and H-400) and the human oral keratinocyte (HOK) cell lines were assessed for GC receptor (GR) expression. The promoting tumor growth effect of GC was evaluated by the CCK-8 assay and flow cytometry. Levels of signaling pathways participants GR, mTOR, and EGFR were determined by quantitative polymerase chain reaction and western blotting. GC increased the proliferation of HNSCC cells in a GR-dependent manner and promoted AKT/mTOR signaling. But GC failed in counteracting the inhibition of rapamycin in the mTOR signaling pathway. Besides, GC also induced resistance to EGFR-targeted drug afatinib through AKT/mTOR instead of the EGFR/ERK signaling pathway. Thus, GCs reduce the efficacy of afatinib on HNSCC, implicating a cautious use of glucocorticoids in clinical practice.