Vitamin C in Cancer: A Metabolomics Perspective

There is an ongoing interest in cellular antioxidants and oxidants as well as cellular mechanisms underlying their effects. Several reports suggest that vitamin C (L-ascorbic acid) functions as a pro-oxidant with selective toxicity against specific types of tumor cells. In addition, reduced glutathione plays an emerging role in reducing oxidative stress due to xenobiotic toxins such as metals and oxidants associated with diseases such as cancer, cardiovascular disease, and stroke. High-dose intravenous vitamin C and intravenous glutathione have been used as complementary, alternative, and adjuvant medicines. Here, we review the molecular mechanisms underlying the regulation of oxidation/reduction systems, focusing on the altered metabolomics profile in cancer cells following treatment with pharmacological vitamin C. This review focuses on the role of vitamin C in energy metabolism in terms of adenosine triphosphate, cysteine, and reduced glutathione levels, affecting cancer cell death.

Systems Biology Perspectives on Vitamin C

From a systems biology perspective, the integrated use of proteomics, genomics, and transcriptomics is extremely important for translational metabolomics-based research

Recently, biological and pre-clinical studies suggest that high dose intravenous vitamin C combined with conventional chemotherapy agent synergistically increase the effectiveness of cancer therapy. (Espey et al., 2011; Hoffer et al., 2015). A phase I study states that high dose intravenous vitamin C in combination with gemcitabine and erlotinib in patients with metastatic pancreatic cancer did not reveal increased toxicity (Monti et al., 2012). In view of the metabolic effect, we conclude that vitamin C plays a key role in the challenges associated with glucose and GSH metabolism (Figure 1 and Table 2). Vitamin C induces high ROS level and oxidation of GSH. Accompanied by direct glutathionylation of GAPDH in glycolysis, glucose metabolism was altered by vitamin C treatment. Furthermore, changes in reduced glutathione ratio triggered by vitamin C resulted in altered GSH metabolism via de novo synthesis. From the information available, it seems clear that vitamin C is involved in a variety of oxidative mechanisms. Therefore, vitamin C may be an adjuvant medicine combined with conventional chemotherapy drug to induce cancer cell death. In the future, another issue pertaining to vitamin C is whether its use as an adjuvant medicine is valid in all populations or only in some populations depending on the range of intakes. Therefore, further studies are required to identify the molecular targets of vitamin C sensitivity such as transporter.