Glyoxalase-1 Inhibition Leads to Ferroptosis Induction in Lung Cancer Cells: A Dual Mechanism of Action of Hydroxamic Acids Derived from Cysteine.
1/5 보강
Lung cancer remains a leading cause of cancer-related mortality worldwide, underscoring the need for novel therapeutic strategies.
APA
Martínez-Miranda J, Aguilar-Cázares D, et al. (2026). Glyoxalase-1 Inhibition Leads to Ferroptosis Induction in Lung Cancer Cells: A Dual Mechanism of Action of Hydroxamic Acids Derived from Cysteine.. ChemMedChem, 21(1), e202500804. https://doi.org/10.1002/cmdc.202500804
MLA
Martínez-Miranda J, et al.. "Glyoxalase-1 Inhibition Leads to Ferroptosis Induction in Lung Cancer Cells: A Dual Mechanism of Action of Hydroxamic Acids Derived from Cysteine.." ChemMedChem, vol. 21, no. 1, 2026, pp. e202500804.
PMID
41319338 ↗
Abstract 한글 요약
Lung cancer remains a leading cause of cancer-related mortality worldwide, underscoring the need for novel therapeutic strategies. In this study, three hydroxamic acids derived from L-cysteine are synthesized to explore their biological dual effect as Glyoxalase 1 (Glo-1) inhibitors and ferroptosis inducers. Among the synthesized derivates, compound 2 exhibited the highest inhibitory potency against Glo-1 and is the most potent compound against nonsmall cell lung cancer cell lines. For this compound, an increase in intracellular reactive oxygen species (ROS), depletion of intracellular reduced glutathione (GSH) levels, and induced morphological changes is observed that correspond to ferroptosis. Furthermore, these effects are reversed by Liproxstatin-1, a potent and selective ferroptosis inhibitor. Acute and subacute toxicological assays in mice showed mild toxicity (LD > 2000 mg kg) and moderate organ damage. These in vitro and in vivo findings suggest that ferroptosis induction may serve as a side effect of Glo-1 inhibition, making compound 2 a promising lead for further development and optimization.
🏷️ 키워드 / MeSH 📖 같은 키워드 OA만
- Ferroptosis
- Humans
- Lactoylglutathione Lyase
- Animals
- Mice
- Lung Neoplasms
- Antineoplastic Agents
- Cysteine
- Hydroxamic Acids
- Reactive Oxygen Species
- Enzyme Inhibitors
- Structure-Activity Relationship
- Drug Screening Assays
- Antitumor
- Dose-Response Relationship
- Drug
- Molecular Structure
- Cell Line
- Tumor
- Cell Proliferation
- cysteine derivatives
- ferroptosis induction
- glyoxalase.1 inhibition
🏷️ 같은 키워드 · 무료전문 — 이 논문 MeSH/keyword 기반
- A Phase I Study of Hydroxychloroquine and Suba-Itraconazole in Men with Biochemical Relapse of Prostate Cancer (HITMAN-PC): Dose Escalation Results.
- Self-management of male urinary symptoms: qualitative findings from a primary care trial.
- Clinical and Liquid Biomarkers of 20-Year Prostate Cancer Risk in Men Aged 45 to 70 Years.
- Diagnostic accuracy of Ga-PSMA PET/CT versus multiparametric MRI for preoperative pelvic invasion in the patients with prostate cancer.
- Association of patient health education with the postoperative health related quality of life in low- intermediate recurrence risk differentiated thyroid cancer patients.
- Early local immune activation following intra-operative radiotherapy in human breast tissue.