ArticleCancer medicine2015
Restoring physiological levels of ascorbate slows tumor growth and moderates HIF-1 pathway activity in Gulo(-/-) mice.
Article in Cancer medicine, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers, 1 of them a synthesis that pooled it.
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Who cites it
36 citing papers in PubMed, 1 synthesis or guideline pooled it, 63 citations in OpenAlex.
- Circulating vitamin C concentration and risk of cancers: a Mendelian randomization study.BMC medicine · 2021Pooled it
- Beyond redox: vitamin C in signaling, epigenetic regulation and protein modification-relevance to cancer therapy.Clinical epigenetics · 2026Review
- High-dose vitamin C: A promising anti-tumor agent, insight from mechanisms, clinical research, and challenges.Genes & diseases · 2026Review
- The physiological functions of ascorbate in the development of cancer.Disease models & mechanisms · 2025Review
- High-dose Ascorbate Exhibits Anti-proliferative and Anti-invasive Effects Dependent on PTEN/AKT/mTOR Pathway in Endometrial CancerInternational journal of biological sciences · 2025Article
- Vitamin C: From nutrition to oxygen sensing and epigenetics.Redox biology · 2023Article
- Genetically predicted vitamin C levels significantly affect patient survival and immunotypes in multiple cancer types.Frontiers in immunology · 2023Article
- High-Dose Vitamin C for Cancer Therapy.Pharmaceuticals (Basel, Switzerland) · 2022Review
- Increased Ascorbate Content of Glioblastoma Is Associated With a Suppressed Hypoxic Response and Improved Patient Survival.Frontiers in oncology · 2022Article
- Vitamin C deficiency reveals developmental differences between neonatal and adult hematopoiesis.Frontiers in immunology · 2022Article
- Inhibition of the HIF-1 Survival Pathway as a Strategy to Augment Photodynamic Therapy Efficacy.Methods in molecular biology (Clifton, N.J.) · 2022Article
- Ascorbate is a multifunctional micronutrient whose synthesis is lacking in primates.Journal of clinical biochemistry and nutrition · 2021Article
- Epigenetic Regulation of Genomic Stability by Vitamin C.Frontiers in genetics · 2021Review
- Natural products as a means of overcoming cisplatin chemoresistance in bladder cancer.Cancer drug resistance (Alhambra, Calif.) · 2021Review
- The Role of 2-Oxoglutarate Dependent Dioxygenases in Gliomas and Glioblastomas: A Review of Epigenetic Reprogramming and Hypoxic Response.Frontiers in oncology · 2021Review
- 2-Oxoglutarate-dependent dioxygenases in cancer.Nature reviews. Cancer · 2020Review
- Nuclear and Cytoplasmic Functions of Vitamin C.Chemical research in toxicology · 2020Review
- HVEM/HIF-1α promoted proliferation and inhibited apoptosis of ovarian cancer cells under hypoxic microenvironment conditions.Journal of ovarian research · 2020Article
- Targeting cancer vulnerabilities with high-dose vitamin C.Nature reviews. Cancer · 2019Review
- Activation of the hypoxia pathway in breast cancer tissue and patient survival are inversely associated with tumor ascorbate levels.BMC cancer · 2019Article
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Hypoxia-inducible factor-1 (HIF-1) governs cellular adaption to the hypoxic microenvironment and is associated with a proliferative, metastatic, and treatment-resistant tumor phenotype. HIF-1 levels and transcriptional activity are regulated by proline and asparagine hydroxylases, which require ascorbate as cofactor. Ascorbate supplementation reduced HIF-1 activation in vitro, but only limited data are available in relevant animal models. There is no information of the effect of physiological levels of ascorbate on HIF activity and tumor growth, which was measured in this study. C57BL/6 Gulo(-/-) mice (a model of the human ascorbate dependency condition) were supplemented with 3300 mg/L, 330 mg/L, or 33 mg/L of ascorbate in their drinking water before and during subcutaneous tumor growth of B16-F10 melanoma or Lewis lung carcinoma (LL/2). Ascorbate levels in tumors increased significantly with elevated ascorbate intake and restoration of wild-type ascorbate levels led to a reduction in growth of B16-F10 (log phase P < 0.001) and LL/2 tumors (lag growth P < 0.001, log phase P < 0.05). Levels of HIF-1α protein in tumors decreased as dietary ascorbate supplementation increased for both tumor models (P < 0.001). Similarly, tumor ascorbate was inversely correlated with levels of the HIF-1 target proteins CA-IX, GLUT-1, and VEGF in both B16-F10 and LL/2 tumors (P < 0.05). The extent of necrosis was similar between ascorbate groups but varied between models (30% for B16-F10 and 21% for LL/2), indicating that ascorbate did not affect tumor hypoxia. Our data support the hypothesis that restoration of optimal intracellular ascorbate levels reduces tumor growth via moderation of HIF-1 pathway activity.
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