Hyper-energy metabolism of oxidative phosphorylation and enhanced glycolysis contributes to radioresistance in glioma cells.

IF 3.6 3区 生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY
Free Radical Research Pub Date : 2025-02-01 Epub Date: 2025-01-28 DOI:10.1080/10715762.2025.2456740
Yogesh Rai, Ankit Kumar Tiwari, Rakesh Pandey, B S Dwarakanath, Anant Narayan Bhatt
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引用次数: 0

Abstract

The concept of dual-state hyper-energy metabolism characterized by elevated glycolysis and OxPhos has gained considerable attention during tumor growth and metastasis in different malignancies. However, it is largely unknown how such metabolic phenotypes influence the radiation response in aggressive cancers. Therefore, the present study aimed to investigate the impact of hyper-energy metabolism (increased glycolysis and OxPhos) on the radiation response of a human glioma cell line. Modulation of the mitochondrial electron transport chain was carried out using a 2,4-dinitrophenol (DNP). Metabolic characterization was carried out by assessing glucose uptake, lactate production, mitochondrial mass, membrane potential, and ATP production. The radiation response was examined by cell growth, clonogenic survival, and cell death assays. Macromolecular oxidation was assessed by DNA damage, lipid peroxidation, and protein carbonylation assay. Hypermetabolic OPM-BMG cells exhibited a significant increase in glycolysis and OxPhos following irradiation as compared to the parental BMG-1 cells. Enhanced radioresistance of OPM-BMG cells was evidenced by the increase in α/β ratio (9.58) and D1 dose (4.18 Gy) as compared to 4.36 and 2.19 Gy in BMG-1 cells respectively. Moreover, OPM-BMG cells were found to exhibit increased resistance against radiation-induced cell death, and macromolecular oxidation as compared to BMG-1 cells. Inhibition of glycolysis and mitochondrial complex-II significantly enhanced the radiosensitivity of OPM-BMG cells compared to BMG-1 cells. Our results demonstrate that the hyper-energy metabolism of increased glycolysis and OxPhos confer radioresistance. Consequently targeting glycolysis and OxPhos in combination with radiation may overcome therapeutic resistance in aggressive cancers like glioma.

氧化磷酸化的高能量代谢和糖酵解的增强有助于胶质瘤细胞的辐射抗性。
目的以糖酵解和OxPhos升高为特征的双态高能量代谢概念在不同恶性肿瘤的生长和转移过程中得到了广泛关注。然而,这种代谢表型如何影响侵袭性癌症的辐射反应在很大程度上是未知的。因此,本研究旨在探讨高能量代谢(糖酵解和OxPhos增加)对人类胶质瘤细胞系辐射反应的影响。方法采用2,4-二硝基苯酚(DNP)对线粒体电子传递链进行调控。代谢特性通过评估葡萄糖摄取、乳酸生成、线粒体质量、膜电位和ATP生成来进行。通过细胞生长、克隆存活和细胞死亡试验来检测辐射反应。通过DNA损伤、脂质过氧化和蛋白质羰基化测定来评估大分子氧化。结果与亲本BMG-1细胞相比,低代谢OPM-BMG细胞在辐照后糖酵解和OxPhos水平显著升高。与BMG-1细胞相比,OPM-BMG细胞的α/β比(9.58)和D1剂量(4.18 Gy)分别增加了4.36和2.19 Gy,表明OPM-BMG细胞的辐射抗性增强。此外,与BMG-1细胞相比,OPM-BMG细胞对辐射诱导的细胞死亡和大分子氧化表现出更强的抵抗力。与BMG-1细胞相比,抑制糖酵解和线粒体复合物- ii可显著增强OPM-BMG细胞的放射敏感性。结论糖酵解和氧磷的高能量代谢导致了辐射抵抗。因此,靶向糖酵解和OxPhos联合放疗可能克服侵袭性癌症如胶质瘤的治疗耐药性。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
Free Radical Research
Free Radical Research 生物-生化与分子生物学
CiteScore
6.70
自引率
0.00%
发文量
47
审稿时长
3 months
期刊介绍: Free Radical Research publishes high-quality research papers, hypotheses and reviews in free radicals and other reactive species in biological, clinical, environmental and other systems; redox signalling; antioxidants, including diet-derived antioxidants and other relevant aspects of human nutrition; and oxidative damage, mechanisms and measurement.
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