As a powerful antioxidant, vitamin C protects cells from oxidative damage by inhibiting production of free radicals. However, high levels of vitamin C shows cytotoxicity especially on cancerous cells through generating excessive ROS and blocking the energy homeostasis. Although the double-sided character of vitamin C has been extensively studied in many cell types, there is little research on the consequence of vitamin C treatment in stem cells. Here, we identified that high-dose vitamin C shows cellular toxicity on proliferating NSPCs. We also demonstrated that undifferentiated NSPCs are more sensitive to vitamin C-driven DNA damage than differentiated cells, due to higher expression of Glut genes. Finally, we showed that high-dose vitamin C selectively induces DNA damage on cancer stem cells rather than differentiated tumor cells, raising a possibility that vitamin C may be used to target cancer stem cells.

Slow drug release at the tumor tissue and poor tumor penetration are two big challenges for the successful application of nanosystems in tumor therapy. Here, we report that a high concentration of the natural reducing agent vitamin C (VC) triggers rapid extracellular PTX release from PTX-loaded shell-sheddable PEG-SS-PCL micelles (SSM) in tumors in vivo. An in vivo tolerance study showed that VC at a blood concentration of 40mM had little toxicity to nude mice. Notably, SSM rapidly disassembled and released the payloads (Cy5 or PTX) in response to 40mM VC. In vivo near-infrared imaging of tumor-bearing mice showed that with post-injection of VC to establish a blood concentration of 40mM, Cy5 was quickly released from the micelles and diffused deep into the tumor tissue. Biodistribution studies revealed that 6h after the injection of PTX-loaded micelles the highest tumor accumulation was reached, which was set as the injection time for VC. The antitumor efficacy of a combination therapy of PTX-loaded micelles and VC was evaluated in both MCF-7 and U87MG tumor models. In both tumor models, single injections of VC didn't show any antitumor effect, while sequential administration of PTX-loaded SSM and VC exhibited significantly higher tumor inhibition effects and better survival rates as compared to single treatment with PTX-loaded micelles, demonstrating that exogenous administration of VC effectively triggered the release of PTX from SSM in vivo. The combination of reduction-sensitive nanomedicines with exogenous VC appears a promising approach to achieve potent treatment of malignant tumors.

To study the effects of gentamicin in combination with ascorbic acid on septic arthritis, mice were infected with Staphylococcus aureus (S. aureus) and treated with gentamicin, which was given at 5 mg/kg after 24 h of infection, followed by ascorbic acid, given at 20 mg/kg body weight after 2 h of gentamicin treatment. Mice were sacrificed at 3, 9, 15 days post-infection (dpi). Combined treatment of infected mice with gentamicin and ascorbic acid eradicated the bacteria from the blood, spleen and synovial tissue and showed a significant gross reduction in arthritis, reduced serum levels of tumour necrosis factor alpha (TNF-α) and interferon gamma (IFN-γ). S. aureus-infected mice have demonstrated the disturbed antioxidant status measured in terms of cellular antioxidants like reduced glutathione and antioxidant enzymes such as superoxide dismutase (SOD) and catalase. The same were ameliorated when the animals were co-treated with gentamicin along with ascorbic acid.

Vitamins A and C represent unrelated sets of small molecules that are essential to the human diet and have recently been shown to intensify erasure of epigenetic memory in naive embryonic stem cells. These effects are driven by complementary enhancement of the ten-eleven translocation (TET) demethylases - vitamin A stimulates TET expression, whereas vitamin C potentiates TET catalytic activity. Vitamin A and C cosupplementation synergistically enhances reprogramming of differentiated cells to the naive state, but overuse may exaggerate instability of imprinted genes. As such, optimizing their use in culture media will be important for regenerative medicine and mammalian transgenics. In addition, mechanistic perception of how these vitamins interact with the epigenome may be relevant for understanding cancer and improving patient treatment.

This study aims to discuss the remission effect of vitamin C on isoflurane-induced apoptosis of rats and its possible mechanism of action, to provide a theoretical basis for postoperative cognitive impairment. Reactive oxygen species (ROS) detection, adenosine triphosphate (ATP) test, MTT method and Morris water maze were applied for detection tests. For data statistics, double factor analysis of variance (ANOVA) and post hoc Bonferroni test were adopted. It was found that vitamin C could slow down the isoflurane-induced accumulation of ROS in H4-APP cells; moreover, it could relieve the activation of caspase-3 and increase cell survival rate to inhibit the occurrence of apoptosis, indicating that ROS was the source of cell toxicity. On the other hand, vitamin C could protect the cells with its antioxidant effect. It was proved that vitamin C could remit isoflurane-induced apoptosis and relieve the decline in learning and memory ability of rats.

The purpose of this study was to assess the synergistic effect of polydatin and vitamin C on attenuating cardiotoxicity induced by doxorubicin (DOX) in rats. Polydatin could significantly increase the activity of SOD and the heart rate, attenuate myocardial pathological damage, decrease MDA content, slightly increase arterial pressure and GSH-Px activity, reduce intervals of QRS, QT and ST, and lower FFA content. The combination of polydatin and vitamin C could significantly increase arterial pressure and heart rate, decrease QRS interval and slightly reduce ST and QT intervals, significantly attenuate myocardial pathological damage, increase the activities of GSH-Px,T-SOD, Na(+) K(+) -ATPase and Ca(2+) Mg(2+) -ATPase, and elevate PCr and ATP contents, slightly increase ADP and TAN contents and PCr/ATP, and significantly decrease the contents of MDA and FFA, when compared with those in the DOX group. Meanwhile, the improvement effects on FFA content, the activities of ATPase and SOD and contents of ATP and TAN in combination group were more obvious than those in polydatin group; and the improvement effects on arterial pressure, heart rate, interval of QRS, GSH-Px activity, and MDA, ADP and PCr contents in combination group were slightly obvious when compared with those in polydatin group. In addition, the mRNA expression levels of AMPK-α2 and PPAR-α were slightly improved in combination group. The results illustrate that the combination of polydatin and vitamin C has the ability to enhance the myocardial protective effects by its antioxidative effect and improving energy metabolism. This article is protected by copyright. All rights reserved.

BACKGROUND:Decitabine is widely used in the treatment of acute myeloid leukemia (AML) in elderly patients. Low-dose Vitamin C has also been indicated to induce DNA demethylation at the cellular level. However, little is known whether low-dose Vitamin C has a synergistic effect with decitabine in clinic.

METHODS:The effect of combined low-dose Vitamin C and decitabine on cell proliferation, the cell cycle, apoptosis and the expression level and activity of TET2 was investigated in HL60 and NB4 human leukemic cells. Additionally, we analyzed the clinical outcomes of 73 elderly AML patients who received A-DCAG (intravenous Vitamin C [IVC] plus DCAG [n = 39]) or DCAG (n = 34) treatment.

RESULTS:We found that low-dose Vitamin C and decitabine has a synergistic efficacy on proliferation, apoptosis, TET2 expression and activity, compared to drug-alone treatment in HL60 and NB4 cell lines in vitro. In clinic, feasibility and safety evaluations revealed that patients who received A-DCAG regimen have a higher complete remission (CR) rate than those who received the DCAG regimen (79.92% vs. 44.11%; P = 0.004) after one cycle of chemotherapy. The median overall survival (OS) was better in the A-DCAG group compared with the DCAG group (15.3 months vs. 9.3 months, P = 0.039). Patients with adverse cytogenetics did benefit from CR. There was no clinically significant additional toxicity observed with the addition of IVC.

CONCLUSION:On the basis of these results, the addition of IVC at low doses to DCAG appeared to improve CR and prolong OS, compared with DCAG, in elderly patients with AML.

It has been demonstrated that vitamin C exhibits anti-cancer activity in various tumor cell lines; however, its specific mechanism of action remains unknown. Although the diagnosis and therapy of cancer patients have markedly improved in recent years, safer and more cost-effective treatments are still required. Therefore, the present study examined the effect of vitamin C on the induction of cell death in gastric cancer and its underlying mechanism of action. It was observed that the cytotoxicity of vitamin C on the human gastric cancer cell line AGS is dependent on the apoptotic pathway, including caspase cascades, but not on the necroptotic pathway. It was demonstrated that the vitamin C-induced calcium influx and ROS generation have critical roles in the induction of apoptosis. Furthermore, vitamin C treatment depleted adenosine triphosphate (ATP) production in AGS cells, and the autophagy pathway may be involved in this process. Taken together, the current study suggests that a high dose of vitamin C may induce gastric cancer cell apoptosis through the dysfunction of mitochondria, including calcium influx, reactive oxygen species generation and ATP depletion.

Observational studies have found a protective effect of vitamin C on cardiovascular health. However, results are inconsistent, and residual confounding by fiber might be present. The aim of this study was to assess the association of vitamin C with the incidence of cardiovascular disease (CVD) and cardiovascular mortality (CVM) while accounting for fiber intake and adherence to the Mediterranean dietary pattern. We followed up 13,421 participants in the Seguimiento Universidad de Navarra (University of Navarra follow-up) (SUN) cohort for a mean time of 11 years. Information was collected at baseline and every two years through mailed questionnaires. Diet was assessed with a validated semi-quantitative food frequency questionnaire. Incident CVD was defined as incident fatal or non-fatal myocardial infarction, fatal or non-fatal stroke, or death due to any cardiovascular cause. CVM was defined as death due to cardiovascular causes. Events were confirmed by physicians in the study team after revision of medical records. Cox proportional hazard models were fitted to assess the associations of (a) energy-adjusted and (b) fiber-adjusted vitamin C intake with CVD and CVM. We found energy-adjusted vitamin C was inversely associated with CVD and CVM after adjusting for several confounding factors, including fiber from foods other than fruits and vegetables, and adherence to the Mediterranean dietary pattern. On the other hand, when vitamin C was adjusted for total fiber intake using the residuals method, we found a significant inverse association with CVM (HR (95% confidence interval (CI)) for the third tertile compared to the first tertile, 0.30 (0.12-0.72), but not with CVD in the fully adjusted model.

This review is directed to the redox-modulating properties and anticancer effect of vitamin K. The concept is focused on two aspects: (i) redox-cycle of vitamin K and its effect on the calcium homeostasis,"oncogenic"and"onco-suppressive"reactive oxygen species and the specific induction of oxidative stress in cancer; (ii) vitamin K plus C as a powerful redox-system, which forms a bypass between mitochondrial complexes II and III and thus prevents mitochondrial dysfunction, restores oxidative phosphorylation and aerobic glycolysis, modulates the redox-state of endogenous redox-pairs, eliminates the hypoxic environment of cancer cells and induces cell death. The analyzed data suggest that vitamin C&K can sensitize cancer cells to conventional chemotherapy, which allows achievement of a lower effective dose of the drug and minimizing the harmful side-effects. The review is intended for a wide audience of readers - from students to specialists in the field.