Glutamine Transporter SLC1A5 Regulates Ionizing Radiation-Derived Oxidative Damage and Ferroptosis

Figure 1

A combination of RT and ferroptosis inducer promotes ferroptotic cell death in the liver tumor cell lines. (a, b) Flow cytometry revealed a significant increase in normalized MFI of lipid peroxidation in SMMC-7721 cells treated with RT (8 Gy) after pretreatment with erastin (25 μM). (c, d) In HepG2-IRR cells, RT (8 Gy) in combination with Erastin (25 μM) enhances the normalized MFI of lipid peroxidation as determined by flow cytometry. (e) After Erastin (25 μM) stimulation, the hierarchical clustering of targeted metabolic comparing HepG2-IRR cells and wild-type HepG2 cells indicates a noticeable increase in amino acid content. (f) Glutamine is essential for SMMC-7721 cell survival, and glutamine starvation induces ferroptosis in SMMC-7721 cells which can be reversed by ferr-1. Erastin: 25 μM; Ferr-1: 1 μM. Magnification: 20X; scale bar: 50 μM. (g, h) The sensitized ferroptosis effect of glutamine deprivation is reversed by glutamine supplementation. Huh7, Huh6, HepG2, and HT1080 cell lines are more susceptible to ferroptotic cell death after being treated with RSL3 (2.5 μM) and glutamine deprivation for 24 hours, and glutamine supplementation can entirely reverse this effect. Abbreviations: RT: radiotherapy; IRR: irradiation-resistant; MFI: mean fluorescence intensity; AFGs: amino acid-ferroptosis genes. .

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