Shams El Dine Rasha S, Youseef Heba T, Awaad Ashraf K, Hammoury Sabahh I, Mohamed Ehab I
Medical Biophysics Department, Medical Research Institute, Alexandria University, Alexandria, Egypt.
Biochemistry and Molecular Biology Department, Alexandria University, Alexandria, Egypt.
Sci Rep. 2025 Apr 29;15(1):15077. doi: 10.1038/s41598-025-96697-x.
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.
白血病是最常见的严重且危及生命的癌症类型，需要立即开始治疗。抗坏血酸（AsA），俗称维生素C，因其抗氧化活性作为人类恶性肿瘤的潜在治疗方法而受到关注。在本研究中，THP-1单核细胞系用两种剂量的AsA处理：低剂量（L-AsA，2.5μg/mL）和高剂量（H-AsA，5μg/mL），而K562淋巴细胞系用两种剂量的AsA处理：低剂量（L-AsA，4μg/mL）和高剂量（H-AsA，8μg/mL）。在24小时的孵育期后，所有细胞暴露于不同剂量的X射线辐射（2、4、8Gy）。使用MTT法评估AsA处理的THP-1和K562细胞的活力。此外，我们评估了细胞凋亡、自噬、增殖、细胞周期进程、缺氧诱导因子（HIF-1）、丙二醛（MDA）和总抗氧化能力（TAC）。我们的研究表明，AsA与X射线辐射联合使用可诱导人白血病THP-1细胞发生显著凋亡，并显著降低Ki67水平。此外，X射线辐射导致DNA损伤，使THP-1细胞的细胞周期停滞在G0/G1期。此外，AsA显著降低了HIF-1水平，而HIF-1水平对缺氧条件下肿瘤细胞的存活至关重要。我们还发现，AsA与X射线辐射联合给药对THP-1和K562细胞具有协同和剂量依赖性作用。值得注意的是，L-AsA与2Gy X射线辐射联合使用比单独使用8Gy X射线辐射显示出更明显的效果。这些结果表明，AsA对白血病细胞具有有前景的抗增殖、促凋亡和自噬作用。此外，与AsA联合使用时，X射线辐射的剂量可能会降低，以尽量减少其潜在的副作用。
