Radiation therapy is employed in treating various cancer types. However, depending on the type and stage of cancer, its benefits can be limited, and it may cause serious side effects that detrimentally affect the quality of life (QOL) for the patient. Preventing the side effects of radiation therapy can enhance the response to cancer treatment and improve the patient’s QOL. Independently, vitamin C and hydrogen have demonstrated potential in reducing the side effects of anticancer drugs and radiation therapy. Furthermore, both have been postulated to possess direct anticancer properties. However, the effects of their combined therapy remain underexplored. This study investigates the hypothesis that combining vitamin C and hydrogen efficiently prevents radiation-induced injuries. Survival rates were investigated in cancer cell lines (MDA-MB231 and GL261) and normal cells (HUVEC) treated with hydrogen, vitamin C and irradiation. Apoptosis was assessed using the FLICA test, and EMT gene expression was elucidated via the qPCR technique. In the normal cell line, the introduction of vitamin C and hydrogen to the culture medium boosted survival rates, exhibiting a radioprotective effect upon irradiation. In contrast, cancer cells showed a decreased survival rate with the introduction of vitamin C and hydrogen, which was further diminished with irradiation. Treated cancer cells showed signs of apoptosis. Caspase activity in viable cells was reduced by the combination treatment with vitamin C and hydrogen. Additionally, glioblastoma cells treated with this combination showed reduced EMT gene expression. This study reveals that a combined therapy of hydrogen and vitamin C offers radioprotective effects on normal cells and exerts direct anticancer effects on cancer cells, while also amplifying the anticancer effects of radiation. Importantly, this combined therapy attenuated the radiation-induced EMT signature in the GL261 murine glioma cell line, suggesting potential in diminishing treatment resistance and tumor invasion.

Background: Radiation therapy is widely used to treat cancer but frequently causes normal tissue toxicities that compromise patients’ quality of life, highlighting the need for strategies that protect healthy tissue without reducing antitumor efficacy. Here, we investigated whether a redox-modulating intervention combining vitamin C and molecular hydrogen could mitigate radiation-induced injury while preserving or enhancing anticancer effects. Methods: Normal endothelial cells together with breast cancer and glioma cell lines were treated with vitamin C and hydrogen before and/or after irradiation, followed by assessments of cell viability, apoptosis, reactive oxygen species (ROS), and epithelial–mesenchymal transition (EMT)-associated gene expression. To explore the potential clinical relevance of these findings, two patients undergoing radiotherapy received the combination treatment as supportive care. Results: In normal cells, the combination treatment increased post-irradiation viability and reduced intracellular ROS levels, consistent with a cytoprotective antioxidant effect. In contrast, cancer cells exhibited reduced viability and increased apoptosis following the combined treatment, effects that were further enhanced by irradiation. In glioma cells, the combination treatment also suppressed the expression of EMT-associated genes. In the two clinical cases, improvements in radiation-associated toxicities were observed, including dermatitis, oral mucositis, gastrointestinal symptoms, and hair loss, along with improved treatment tolerability. Conclusions: Collectively, these exploratory findings suggest that the combination of vitamin C and hydrogen produces distinct responses among the cell models examined, with increased viability and reduced ROS in HUVECs and reduced viability, increased apoptosis, and altered EMT-associated gene expression in the cancer cell lines. These findings warrant further investigation of this combination as a potential adjunct to radiotherapy.