ArticleChemical research in toxicology2012
Nitric oxide produced endogenously is responsible for hypoxia-induced HIF-1α stabilization in colon carcinoma cells.
Article in Chemical research in toxicology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
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Who cites it
30 citing papers in PubMed, 48 citations in OpenAlex.
- Photothermal therapy triggering organelle stress and metabolic reprogramming to potentiate antitumor immunity.Frontiers in immunology · 2026Review
- Advances in Metabolic Reprogramming and Immune Regulatory Mechanisms in Lung Cancer.Oncology research · 2026Review
- Contribution and Regulation of HIF-1α in Testicular Injury Induced by Diabetes Mellitus.Biomolecules · 2025Review
- Development of an Asymmetric Alginate Hydrogel Loaded with S-Nitrosoglutathione and Its Application in Chronic Wound Healing.Gels (Basel, Switzerland) · 2025Article
- Dissecting the opposing regulatory functions of endogenous nitric oxide production in colorectal cancer initiation, adaptive immune response alterations, and ferroptosis execution.Oncology reviews · 2025Review
- Advances and prospects of RNA delivery nanoplatforms for cancer therapy.Acta pharmaceutica Sinica. B · 2025Review
- The PPARα Regulation of the Gut Physiology in Regard to Interaction with Microbiota, Intestinal Immunity, Metabolism, and Permeability.International journal of molecular sciences · 2022Review
- Gene profiling of SEC13, SMAD7, GHRL, long non-coding RNA GHRLOS, HIF-1α in gastric cancer patients.Scientific reports · 2022Article
- Targeting Metabolic Pathways of Myeloid Cells Improves Cancer Immunotherapy.Frontiers in cell and developmental biology · 2021Review
- The Landscape of Interactions between Hypoxia-Inducible Factors and Reactive Oxygen Species in the Gastrointestinal Tract.Oxidative medicine and cellular longevity · 2021Review
- A divergent mode of activation of a nitrosyl iron complex with unusual antiangiogenic activity.Journal of inorganic biochemistry · 2020Article
- Caveolin-1-Mediated Tumor Suppression Is Linked to Reduced HIF1α S-Nitrosylation and Transcriptional Activity in Hypoxia.Cancers · 2020Article
- Microneedles for transdermal diagnostics: Recent advances and new horizons.Biomaterials · 2020Review
- Autophagy Regulated by Gain of Function Mutant p53 Enhances Proteasomal Inhibitor-Mediated Cell Death through Induction of ROS and ERK in Lung Cancer Cells.Journal of oncology · 2019Article
- Article
- A role for endothelial nitric oxide synthase in intestinal stem cell proliferation and mesenchymal colorectal cancer.BMC biology · 2018Article
- Nitric oxide inhibits ATPase activity and induces resistance to topoisomerase II-poisons in human MCF-7 breast tumor cells.Biochemistry and biophysics reports · 2017Article
- The dynamic role of autophagy and MAPK signaling in determining cell fate under cisplatin stress in osteosarcoma cells.PloS one · 2017Article
- Thiol-Activated HNO Release from a Ruthenium Antiangiogenesis Complex and HIF-1α Inhibition for Cancer Therapy.ACS chemical biology · 2016Article
- Nitric oxide inhibits topoisomerase II activity and induces resistance to topoisomerase II-poisons in human tumor cells.Biochimica et biophysica acta · 2016Article
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 2 countries.
Funding
Abstract
Hypoxia-inducible factor-1α (HIF-1α) is a critical regulator of cellular responses to hypoxia. Under normoxic conditions, the cellular HIF-1α level is regulated by hydroxylation by prolyl hydroxylases (PHDs), ubiquitylation, and proteasomal degradation. During hypoxia, degradation decreases, and its intracellular level is increased. Exogenously administered nitric oxide (NO)-donor drugs stabilize HIF-1α; thus, NO is suggested to mimic hypoxia. However, the role of low levels of endogenously produced NO generated during hypoxia in HIF-1α stabilization has not been defined. Here, we demonstrate that NO and reactive oxygen species (ROS) produced endogenously by human colon carcinoma HCT116 cells are responsible for HIF-1α accumulation in hypoxia. The antioxidant N-acetyl-L-cysteine (NAC) and NO synthase inhibitor N(G)-monomethyl L-arginine (L-NMMA) effectively reduced HIF-1α stabilization and decreased HIF-1α hydroxylation. These effects suggested that endogenous NO and ROS impaired PHD activity, which was confirmed by reversal of L-NMMA- and NAC-mediated effects in the presence of dimethyloxaloylglycine, a PHD inhibitor. Thiol reduction with dithiothreitol decreased HIF-1α stabilization in hypoxic cells, while dinitrochlorobenzene, which stabilizes S-nitrosothiols, favored its accumulation. This suggested that ROS- and NO-mediated HIF-1α stabilization involved S-nitrosation, which was confirmed by demonstrating increased S-nitrosation of PHD2 during hypoxia. Our results support a regulatory mechanism of HIF-1α during hypoxia in which endogenously generated NO and ROS promote inhibition of PHD2 activity, probably by its S-nitrosation.
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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.