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 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.…”

Repurposing Vitamin C for Cancer Treatment: Focus on Targeting the Tumor Microenvironment

“…Its combination with conventional radiotherapy and chemotherapy amplifies the cytotoxicity to cancer cells and reduces the treatment-related side effects and off-target effects. Several reviews have summarized the research in this area [ 105 , 106 ]. Herein, we will focus on combining VitC with novel therapies in cancers and TME.…”