High-dose intravenous vitamin C, a promising multi-targeting agent in the treatment of cancer

Abstract

Mounting evidence indicates that vitamin C has the potential to be a potent anti-cancer agent when administered intravenously and in high doses (high-dose IVC). Early phase clinical trials have confirmed safety and indicated efficacy of IVC in eradicating tumour cells of various cancer types. In recent years, the multi-targeting effects of vitamin C were unravelled, demonstrating a role as cancer-specific, pro-oxidative cytotoxic agent, anti-cancer epigenetic regulator and immune modulator, reversing epithelial-to-mesenchymal transition, inhibiting hypoxia and oncogenic kinase signalling and boosting immune response. Moreover, high-dose IVC is powerful as an adjuvant treatment for cancer, acting synergistically with many standard (chemo-) therapies, as well as a method for mitigating the toxic side-effects of chemotherapy. Despite the rationale and ample evidence, strong clinical data and phase III studies are lacking. Therefore, there is a need for more extensive awareness of the use of this highly promising, non-toxic cancer treatment in the clinical setting. In this review, we provide an elaborate overview of pre-clinical and clinical studies using high-dose IVC as anti-cancer agent, as well as a detailed evaluation of the main known molecular mechanisms involved. A special focus is put on global molecular profiling studies in this respect. In addition, an outlook on future implications of high-dose vitamin C in cancer treatment is presented and recommendations for further research are discussed.

Vitamin C Deficiency in Patients With Acute Myeloid Leukemia

“…Vitamin C has been suggested as a potential anticancer agent, and several preclinical data have recently confirmed its selective cytotoxicity in different human malignancies, both in vitro and in vivo (21)(22)(23). Recently, pharmacological studies have demonstrated that vitamin C may represents a potent anti-cancer agent when administered intravenously and in high doses (24). In this line, Cimmino and colleagues (25), showed that treatment with vitamin C mimics TET2 restoration in Tet2-deficient mouse HSPCs, suppressing human leukemic colony formation, and leukemia progression in primary human leukemia patient-derived xenografts (PDXs).…”

Vitamin C Sensitizes Pancreatic Cancer Cells to Erastin-Induced Ferroptosis by Activating the AMPK/Nrf2/HMOX1 Pathway

“…A growing number of studies during the past decade have demonstrated that pharmacological concentrations of vitamin C are effective in killing cancer cells in vitro and slowing tumor growth in vivo [ 24 , 25 ]. However, the mechanism by which cancer cells are sensitive to vitamin C while normal cells remain resistant is unclear and requires further study.…”

Ascorbate as a Bioactive Compound in Cancer Therapy: The Old Classic Strikes Back

“…Improved study design and better informed studies may now be expected given the new focus on well-performed studies of its fundamental biology. For instance, a recent molecular characterisation of tumour cells has suggested that the susceptibility of these cells to the therapeutic effect of ascorbate alone or in a combined therapy may be modulated by the overexpression or mutation of a suite of specific proteins [26], underscoring the benefits of multitarget therapy. Studies similar to this one have elevated the idea that the beneficial therapeutic properties of ascorbate may be augmented in the presence of other antineoplastic agents, thereby leading to a better clinical outcome and life quality and expectancy of patients.…”