ArticleFrontiers in cell and developmental biology2022
Blockade of GCH1/BH4 Axis Activates Ferritinophagy to Mitigate the Resistance of Colorectal Cancer to Erastin-Induced Ferroptosis.
Article in Frontiers in cell and developmental biology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 134 papers, 2 of them syntheses that pooled it.
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Who cites it
134 citing papers in PubMed, 2 syntheses or guidelines pooled it, 171 citations in OpenAlex.
- Mechanism and role of ferroptosis in the development of gastric cancer.Clinical and experimental medicine · 2025Pooled it
- Review of ferroptosis in colorectal cancer: Friends or foes?World journal of gastroenterology · 2023Pooled it
- Ferroptosis in skeletal muscle: from molecular mechanisms to therapeutic interventions.Journal of orthopaedic translation · 2026Review
- Article
- Cell-Type-Specific Regulation of Ferroptosis in Atherosclerosis: Mechanisms and Therapeutic Potential of Natural Products.Cell biochemistry and function · 2026Review
- Crosstalk between autophagy and ferroptosis in diabetes.Genes & diseases · 2026Review
- CFHR5 promotes colorectal cancer by upregulating COX4I2 to inhibit ferroptosis.Annals of medicine and surgery (2012) · 2026Article
- Ferroptosis in colorectal cancer: Molecular mechanisms and regulatory crosstalk with therapeutic prospects (Review).Oncology reports · 2026Review
- Molecular Effects of Indocyanine Green-Photodynamic Therapy on Programmed Cell Death Pathways in T98G and U-118MG Glioblastoma Cells-An RT-qPCR Study.Current issues in molecular biology · 2026Article
- Traditional Chinese Medicine Targeting Ferroptosis in Cardiovascular Diseases: Advances and Perspectives.Journal of cardiovascular translational research · 2026Review
- Liproxstatin-1 Attenuates Retinal Ischemia-Reperfusion Injury by Suppressing EGR1-Mediated Ferroptosis.Antioxidants (Basel, Switzerland) · 2026Article
- The Mechanism of Ferroptosis and Blood-Brain Barrier Damage in Cerebrovascular Diseases.Biomedicines · 2026Review
- Ferroptosis in cardiovascular diseases: molecular mechanisms and a novel therapeutic target.Molecular biomedicine · 2026Review
- Ferroptosis: The dawn of reversing drug resistance in digestive cancers.Genes & diseases · 2026Review
- Navigating the complexities of ferroptosis in pancreatic ductal adenocarcinoma: roles, mechanisms and potential applications.Cell death discovery · 2026Review
- Research progress on the regulation of ferroptosis in NPC (Review).Oncology reports · 2026Review
- Expression of Antioxidant Defense Genes Determines Synergistic Ferroptosis Induction by the Combination of Erastin and Omega-3 Docosahexaenoic Acid in Prostate Cancer Cells.Doklady. Biochemistry and biophysics · 2026Article
- Interplay between natural killer cells and ferroptosis: novel insights in tumor immunity and therapeutic potential.Cell communication and signaling : CCS · 2026Review
- Consensus Molecules Associated with Parkinson's Disease.Neurology international · 2026Review
- Autophagy regulation of pyroptosis and ferroptosis: a new strategy for colorectal cancer treatment.Apoptosis : an international journal on programmed cell death · 2026Review
74 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
11 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Ferroptosis, a type of cell death triggered by excessive accumulation of iron-dependent lipid peroxidation, possesses an excellent potential in cancer treatment. However, many colorectal cancer (CRC) cell lines are resistant to ferroptosis induced by erastin and RSL3, the classical ferroptotic inducers. Moreover, the underlying mechanism of resistance remains poorly elucidated. This study sought to discover the major factor contributing to ferroptosis resistance in CRC. The study findings will help design strategies for triggering ferroptosis for application in individualized tumor therapy. Here, we show that tetrahydrobiopterin (BH4) determines the sensitivity of CRC cells to ferroptosis induced by erastin. GTP cyclohydrolase-1 (GCH1) is the first rate-limiting enzyme of BH4. Genetic or pharmacological inhibition of GCH1 decreased BH4 and assisted erastin in cell death induction, lipid peroxidation enhancement, and ferrous iron accumulation. BH4 supplementation completely inhibited ferroptotic features resulting from GCH1 knockdown. Unexpectedly, GCH1 knockdown failed to enhance RSL3-induced cell death in CRC. Mechanistically, GCH1 knockdown drastically activated ferritinophagy during erastin treatment rather than RSL3 treatment. Administration of an autophagy inhibitor reversed erastin resistance in GCH1-knockdown cells. GCH1 inhibitor and erastin co-treatment
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.