Role of Vitamin C in Targeting Cancer Stem Cells and Cellular Plasticity

Simple Summary This review is centered on the potential therapeutic utility of vitamin C (VC) in the context of dynamic cancer evolution. Physiologically, VC has dose-dependent roles as both an antioxidant and a pro-oxidant and has been associated with various health benefits, including potential applications in cancer management. Its intriguing ability to selectively target cancer cells has sparked recent research exploring its potential use against cancer stem cells (CSCs), a crucial player in both tumorigenesis and metastasis. CSCs play a pivotal role in tumor progression, metastasis, and resistance to conventional drug treatments. This review seeks to elucidate the underlying mechanisms by which VC effectively targets and reduces the activity of CSCs, thereby providing important insights and rationale for the improvement of anti-cancer therapeutic strategies.Abstract Vitamin C (VC) is an essential nutrient that is vital for maintaining cellular physiology. Interestingly, it functions as either an antioxidant or a pro-oxidant, depending on the concentration used. At high-doses, VC selectively targets various cancer cell types through its pro-oxidant action, while at low-doses, VC enhances anti-tumor immunity by acting as an antioxidant. This versatility makes VC a promising anti-tumor agent for both standalone and combination therapies. Tumors consist of diverse cancer cell subtypes with distinct phenotypic and functional characteristics. In particular, cancer stem cells (CSCs), which are self-renewing multi-potent cells, are responsible for tumor recurrence, metastasis, chemoresistance, and heightened mortality. CSCs are often associated with the epithelial-mesenchymal transition (EMT), which confers increased motility and invasive capabilities that are characteristic of malignant and drug-resistant cells. Thus, eradicating CSC populations is crucial and has led to extensive efforts aimed at identifying medicines that can target them. Recent studies suggest that VC can selectively target CSCs via epigenetic and metabolic pathways in various cancers. Here, we highlight recent progress that has been made in understanding how VC effectively targets CSC evolution, providing a rationale for the use of VC either alone or in combination with other treatments to improve outcomes.