ArticleEBioMedicine2019
Vitamin C supplementation expands the therapeutic window of BETi for triple negative breast cancer.
Article in EBioMedicine, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
16 citing papers in PubMed, 23 citations in OpenAlex.
- Plasma Vitamin C Levels in Distinguishing Benign from Malignant Breast Tumors and Clinical Correlates in Chinese Patients: A Cross-Sectional Study.Breast cancer (Dove Medical Press) · 2026Article
- Therapeutic potentials of natural products for post-traumatic stress disorder: A focus on epigenetics.Chinese herbal medicines · 2025Review
- The protective role of prenatal administration of ascorbic acid on autistic-like behavior in a rat model of autism.IBRO neuroscience reports · 2024Article
- Joint multi-omics discriminant analysis with consistent representation learning using PANDA.Research square · 2024Article
- TRIM24 is critical for the cellular response to DNA double-strand breaks through regulating the recruitment of MRN complex.Oncogene · 2023Article
- Repurposing Vitamin C for Cancer Treatment: Focus on Targeting the Tumor Microenvironment.Cancers · 2022Review
- The mmu_circRNA_37492/hsa_circ_0012138 function as potential ceRNA to attenuate obstructive renal fibrosis.Cell death & disease · 2022Article
- Review
- Role of Vitamin C in Selected Malignant Neoplasms in Women.Nutrients · 2022Review
- Neonatal Vitamin C and Cysteine Deficiencies Program Adult Hepatic Glutathione and Specific Activities of Glucokinase, Phosphofructokinase, and Acetyl-CoA Carboxylase in Guinea Pigs' Livers.Antioxidants (Basel, Switzerland) · 2021Article
- Achieving clinical success with BET inhibitors as anti-cancer agents.British journal of cancer · 2021Review
- Anticancer Effects of I-BET151, an Inhibitor of Bromodomain and Extra-Terminal Domain Proteins.Frontiers in oncology · 2021Review
- Co-targeting BET bromodomain BRD4 and RAC1 suppresses growth, stemness and tumorigenesis by disrupting the c-MYC-G9a-FTH1axis and downregulating HDAC1 in molecular subtypes of breast cancer.International journal of biological sciences · 2021Article
- Targeting complexes of super-enhancers is a promising strategy for cancer therapy.Oncology letters · 2020Review
- Vitamin C Inhibits Triple-Negative Breast Cancer Metastasis by Affecting the Expression of YAP1 and Synaptopodin 2.Nutrients · 2019Article
- Pro- and Antioxidant Effects of Vitamin C in Cancer in correspondence to Its Dietary and Pharmacological Concentrations.Oxidative medicine and cellular longevity · 2019Review
Corrections and comments
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Authors and funding
12 authors at 1 institution in 1 country.
Funding
Abstract
backgroundBromodomain and extra-terminal inhibitors (BETi) have shown efficacy for the treatment of aggressive triple negative breast cancer (TNBC). However, BETi are plagued by a narrow therapeutic window as manifested by severe toxicities at effective doses. Therefore, it is a limitation to their clinical implementation in patient care.
methodsThe impact of vitamin C on the efficacy of small compounds including BETi was assessed by high-throughput screening. Co-treatment of TNBC by BETi especially JQ1 and vitamin C was evaluated in vitro and in vivo.
findingsHigh-throughput screening revealed that vitamin C improves the efficacy of a number of structurally-unrelated BETi including JQ1, I-BET762, I-BET151, and CPI-203 in treating TNBC cells. The synergy between BETi and vitamin C is due to suppressed histone acetylation (H3ac and H4ac), which is in turn caused by upregulated histone deacetylase 1 (HDAC1) expression upon vitamin C addition. Treatment with JQ1 at lower doses together with vitamin C induces apoptosis and inhibits the clonogenic ability of cultured TNBC cells. Oral vitamin C supplementation renders a sub-therapeutic dose of JQ1 able to inhibit human TNBC xenograft growth and metastasis in mice.
interpretationVitamin C expands the therapeutic window of BETi by sensitizing TNBC to BETi. Using vitamin C as a co-treatment, lower doses of BETi could be used to achieve an increased therapeutic index in patients, which will translate to a reduced side effect profile. FUND: University of Miami Sylvester Comprehensive Cancer Center, Bankhead Coley Cancer Research program (7BC10), Flight Attendant Medical Research Institute, and NIH R21CA191668 (to GW) and 1R56AG061911 (to CW and CHV).
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