Vitamin C, From Supplement to Treatment: A Re-Emerging Adjunct for Cancer Immunotherapy?

Kouakanou, Léonce; Peters, Christian; Brown, Christine E.; Kabelitz, Dieter; Wang, Leo D.

doi:10.3389/fimmu.2021.765906

Cited by 16 publications

(12 citation statements)

References 99 publications

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“…It is generally accepted that ascorbate has a potential therapeutic effect on tumors by generating sustainable ascorbate radical and H 2 O 2 in extracellular fluid ( 17 ). However, the underlying mechanisms for the selective cytotoxicity to cancer cells but not to normal ascorbate cells are not well understood.…”

Section: Discussionmentioning

confidence: 99%

Metabolomic profiling identifies biomarkers and metabolic impacts of surgery for colorectal cancer

et al. 2022

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BackgroundColorectal cancer (CRC) is one of the most common malignant tumors with recurrence and metastasis after surgical resection. This study aimed to identify the physiological changes after surgery and explore metabolites and metabolic pathways with potential prognostic value for CRC.MethodsAn ultra-high-performance liquid chromatography Q-exactive mass spectrometry was used to profile serum metabolites from 67 CRC patients and 50 healthy volunteers. Principal component analysis (PCA) and orthogonal projections to latent structures-discriminant analysis were used to distinguish the internal characteristics of data in different groups. Multivariate statistics were compiled to screen the significant metabolites and metabolic pathways.ResultA total of 180 metabolites were detected. Under the conditions of variable importance in projection >1 and p-value <0.05, 46 differentially expressed metabolites were screened for further pathway enrichment analysis. Based on the Kyoto Encyclopedia of Genes and Genomes database and Small Molecule Pathway Database, three metabolic pathways—arginine and proline metabolism, ascorbate and aldarate metabolism, and phenylalanine metabolism—were significantly altered after surgical resection and identified as associated with the removal of CRC. Notably, gamma-linolenic acid was upregulated in the CRC preoperative patients compared with those in healthy volunteers but returned to healthy levels after surgery.ConclusionThrough serum-based metabolomics, our study demonstrated the differential metabolic characteristics in CRC patients after surgery compared with those before surgery. Our results suggested that metabonomic analysis may be a powerful method for exploring physiological alterations in CRC patients after surgery as well as a useful tool for identifying candidate biomarkers and monitoring disease recurrence.

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Section: Discussionmentioning

confidence: 99%

Metabolomic profiling identifies biomarkers and metabolic impacts of surgery for colorectal cancer

et al. 2022

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“…Ascorbate supplementation is achieved by Vitamin C enrichment into the diet, an essential nutrient whose deficiency associates with several health problems due to its role in demethylation and oxidative stress reactions. However, its anti-neoplastic outcome is still controversial and mostly depends on both delivery and dosage [104]. Interestingly, TET activity, a family of enzymes deputed to the DNA demethylation cycle, is significantly reduced in several solid tumors [105][106][107].…”

Section: Epi-metabolic Diet Approaches In Gi Cancer Patientsmentioning

confidence: 99%

Gastrointestinal Cancer Patient Nutritional Management: From Specific Needs to Novel Epigenetic Dietary Approaches

et al. 2022

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Nutritional habits impinge on the health of the gastrointestinal (GI) tract, contributing to GI disorder progression. GI cancer is a widespread and aggressive tumor sensitive to nutritional changes. Indeed, specific nutritional expedients can be adopted to prevent GI cancer onset and to slow down disease activity. Moreover, the patient’s nutritional status impacts prognosis, quality of life, and chemotherapy tolerance. These patients encounter the highest frequency of malnourishment risk, a condition that can progressively evolve into cachexia. Clinical studies dealing with this topic stressed the importance of nutritional counseling and put under the spotlight nutrient delivery, the type of nutrient supplementation, and timing for the start of nutritional management. A medical practitioner well-prepared on the topic of nutrition and cancer should operate in the clinical team dedicated to these oncological patients. This specific expertise needs to be implemented as soon as possible to adopt nutritional interventions and establish a proper patient-tailored dietary regimen. The nutritional gap closure should be prompt during anticancer treatment to stabilize weight loss, improve treatment tolerability, and ameliorate survival rate. Recently, novel nutritional approaches were investigated to target the bidirectional link between epigenetics and metabolism, whose alteration supports the onset, progression, and therapeutic response of GI cancer patients.

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“…Immune systems that suppress tumorigenesis are also regulated by Asc [ 225 ]. For example, a high dose Asc may demethylate DNA and potentiate anti-PD1 checkpoint inhibition through a synergistic mechanism [ 226 ].…”

Section: Asc In the Prevention And Treatment Of Cancermentioning

confidence: 99%

Ascorbate Is a Primary Antioxidant in Mammals

Fujii

Osaki

2022

Molecules

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Ascorbate (vitamin C in primates) functions as a cofactor for a number of enzymatic reactions represented by prolyl hydroxylases and as an antioxidant due to its ability to donate electrons, which is mostly accomplished through non-enzymatic reaction in mammals. Ascorbate directly reacts with radical species and is converted to ascorbyl radical followed by dehydroascorbate. Ambiguities in physiological relevance of ascorbate observed during in vivo situations could be attributed in part to presence of other redox systems and the pro-oxidant properties of ascorbate. Most mammals are able to synthesize ascorbate from glucose, which is also considered to be an obstacle to verify its action. In addition to animals with natural deficiency in the ascorbate synthesis, such as guinea pigs and ODS rats, three strains of mice with genetic removal of the responsive genes (GULO, RGN, or AKR1A) for the ascorbate synthesis have been established and are being used to investigate the physiological roles of ascorbate. Studies using these mice, along with ascorbate transporter (SVCT)-deficient mice, largely support its ability in protection against oxidative insults. While combined actions of ascorbate in regulating epigenetics and antioxidation appear to effectively prevent cancer development, pharmacological doses of ascorbate and dehydroascorbate may exert tumoricidal activity through redox-dependent mechanisms.

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Vitamin C, From Supplement to Treatment: A Re-Emerging Adjunct for Cancer Immunotherapy?

Cited by 16 publications

References 99 publications

Metabolomic profiling identifies biomarkers and metabolic impacts of surgery for colorectal cancer

Metabolomic profiling identifies biomarkers and metabolic impacts of surgery for colorectal cancer

Gastrointestinal Cancer Patient Nutritional Management: From Specific Needs to Novel Epigenetic Dietary Approaches

Ascorbate Is a Primary Antioxidant in Mammals

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