Radiation-Induced Lipid Peroxidation Triggers Ferroptosis and Synergizes with Ferroptosis Inducers
Ling F. Ye(Columbia University), Kunal Chaudhary(Columbia University), Fereshteh Zandkarimi(Columbia University), Andrew Harken(Columbia University Irving Medical Center), Connor J. Kinslow(Columbia University), Pavan S. Upadhyayula(Neurological Surgery), Athanassios Dovas(Columbia University), Dominique Higgins(Neurological Surgery), Huı Tan(Columbia University), Yan Zhang(Columbia University), Manuela Buonanno(Columbia University Irving Medical Center), Tony J. C. Wang(Columbia University Irving Medical Center), Tom K. Hei(Columbia University Irving Medical Center), Jeffrey N. Bruce(Neurological Surgery), Peter Canoll(Columbia University Irving Medical Center), Simon K. Cheng(Columbia University Irving Medical Center), Brent R. Stockwell(Columbia University Irving Medical Center)
Cited by 512Open Access
Abstract
inhibition or GPX4 inhibition synergize with radiation to induce ferroptosis in several cancer types by enhancing cytoplasmic lipid peroxidation but not increasing DNA damage or caspase activation. Ferroptosis inducers synergized with cytoplasmic irradiation, but not nuclear irradiation. Finally, administration of ferroptosis inducers enhanced the antitumor effect of radiation in a murine xenograft model and in human patient-derived models of lung adenocarcinoma and glioma. These results suggest that ferroptosis inducers may be effective radiosensitizers that can expand the efficacy and range of indications for radiation therapy.
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