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为降低放射治疗风险,抗坏血酸在不同细胞系中的潜在治疗作用。

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

作者信息

Shams El Dine Rasha S, Youseef Heba T, Awaad Ashraf K, Hammoury Sabahh I, Mohamed Ehab I

机构信息

Medical Biophysics Department, Medical Research Institute, Alexandria University, Alexandria, Egypt.

Biochemistry and Molecular Biology Department, Alexandria University, Alexandria, Egypt.

出版信息

Sci Rep. 2025 Apr 29;15(1):15077. doi: 10.1038/s41598-025-96697-x.

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.

摘要

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。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1f5a/12041364/a72af54ca55b/41598_2025_96697_Fig1_HTML.jpg

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