Authors
Gyeongmi Kim, Se-Kyeong Jang, Do-Gyeong Kim, Hyunggee Kim, Jungil Hong, In-Chul Park, Hyeon-Ok Jin
Published in
Medical oncology (Northwood, London, England). Volume 43. Issue 11. Sep 25, 2026. Epub Sep 25, 2026.
Abstract
Ferroptosis, an iron-dependent regulated cell death driven by lipid peroxidation, has emerged as a promising therapeutic target for cancer. Although lapatinib has been reported to induce ferroptosis in several cancer types, we found that it exerts a ferroptosis-suppressive effect under cysteine deprivation. Lapatinib alone induced a mild ferroptotic phenotype (< 10% cell death), accompanied by increased intracellular reactive oxygen species (ROS) generation, lipid peroxidation, and intracellular labile iron (Fe²⁺) accumulation. In contrast, under cysteine deprivation, lapatinib markedly attenuated ferroptotic cell death by suppressing intracellular ROS generation and lipid peroxidation without reducing intracellular Fe²⁺ accumulation. Lapatinib attenuated cysteine deprivation-induced ferroptosis despite further reductions of glutathione (GSH) levels and glutathione peroxidase 4 (GPX4) expression. Moreover, lapatinib also suppressed ferroptosis induced by the direct GPX4 inhibitor RSL3. Lapatinib attenuated cysteine deprivation-induced mitochondrial responses, as evidenced by reduced mitochondrial membrane potential hyperpolarization and oxygen consumption. Collectively, these results demonstrate that lapatinib exerts context-dependent effects, suppressing cysteine deprivation- induced ferroptosis despite inducing a mild ferroptotic phenotype when used alone.
PMID:
42789174
Bibliographic data and abstract were imported from PubMed on 26 Sep 2026.
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