Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

Hydrogen and Vitamin C Combination Therapy: A Novel Method of Radioprotection

Version 1 : Received: 18 December 2023 / Approved: 18 December 2023 / Online: 19 December 2023 (05:19:37 CET)

How to cite: Miyakawa, M.; Zhang, S.; Behnan, J.; Morganti, C.; Ito, K.; Isaksn, P.; Miyakawa, A.; Uhlen, P. Hydrogen and Vitamin C Combination Therapy: A Novel Method of Radioprotection. Preprints 2023, 2023121369. https://doi.org/10.20944/preprints202312.1369.v1 Miyakawa, M.; Zhang, S.; Behnan, J.; Morganti, C.; Ito, K.; Isaksn, P.; Miyakawa, A.; Uhlen, P. Hydrogen and Vitamin C Combination Therapy: A Novel Method of Radioprotection. Preprints 2023, 2023121369. https://doi.org/10.20944/preprints202312.1369.v1

Abstract

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.

Keywords

Hydrogen; vitamin C; cancer treatment; radioprotection; HUVEC; MDA-MB-231; GL261; apoptosis; FLICA; EMT gene expression

Subject

Medicine and Pharmacology, Complementary and Alternative Medicine

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