The potentially therapeutic effects of ascorbic acid in different cell line in attempt to reduce the risk of radiation therapy

Abstract

Abstract Leukemia is the most common type of serious, life-threatening cancer that requires the immediate initiation of therapy. Ascorbic acid (AsA), commonly known as Vitamin C, has been gaining attention due to its antioxidant activity as a potential treatment for human malignancies. In this study, the THP-1 monocytic cell line was treated with two doses of AsA: a low dose (L-AsA, 2.5 µg/mL) and a high dose (H-AsA, 5 µg/mL), while the K562 lymphocytic cell line was treated with two doses of AsA: a low dose (L-AsA, 4 µg/mL) and a high dose (H-AsA, 8 µg/mL). After a 24-h incubation period, all cells were exposed to different doses of X-radiation (2, 4, 8 Gy). The viability of THP-1 and K562 treated by AsA was assessed using the MTT assay. Additionally, we evaluated apoptosis, autophagy, proliferation, cell cycle progression, hypoxia-inducible factor (HIF-1), malondialdehyde (MDA), and total antioxidant capacity (TAC). Our study demonstrated that AsA, in combination with X-radiation, induced significant apoptosis and notably reduced Ki67 levels in human leukemia THP-1 cells. Furthermore, X-radiation caused DNA damage, leading to cell cycle arrest at the G0/G1 phase in THP-1 cells. Moreover, AsA significantly reduced HIF-1 levels, which are essential for the survival of tumor cells in hypoxic conditions. We also found that the administration of AsA in combination with X-radiation had a synergistic and dose-dependent effect on THP-1 and K562 cells. Notably, the combination of L-AsA with 2 Gy X-radiation showed a more pronounced effect than 8 Gy X-radiation alone. These results suggest that AsA has promising anti-proliferative, pro-apoptotic, and autophagic effects on leukemic cells. Furthermore, the dose of X-radiation may be reduced when combined with AsA in an effort to minimize its potential side effects.