金霉素 A 重塑新陈代谢并增加氧化应激,从而阻碍胶质母细胞瘤的进展

IF 4.9 2区 医学 Q1 CHEMISTRY, MEDICINAL Marine Drugs Pub Date : 2024-08-29 DOI:10.3390/md22090391
Dong-Ni Liu, Wen-Fang Zhang, Wan-Di Feng, Shuang Xu, Dan-Hong Feng, Fu-Hang Song, Hua-Wei Zhang, Lian-Hua Fang, Guan-Hua Du, Yue-Hua Wang
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引用次数: 0

摘要

胶质母细胞瘤是中枢神经系统中最主要、侵袭性极强的原发性肿瘤,其代谢异常。我们之前的研究表明,金霉素 A(Chr-A)可抑制胶质母细胞瘤在体外和体内的发展。然而,Chr-A能否抑制原位胶质母细胞瘤以及它是如何重塑新陈代谢的仍不清楚。在这项研究中,Chr-A明显抑制了颅内U87胶质瘤的发展。气流辅助解吸电喷雾质谱成像(AFADESI-MSI)结果表明,Chr-A改善了胶质母细胞瘤小鼠的异常代谢。Chr-A 对谷氨酰胺酶(GLS)、谷氨酸脱氢酶 1(GDH1)、己糖激酶 2(HK2)和葡萄糖-6-磷酸脱氢酶(G6PD)等关键酶进行了调节。Chr-A 进一步改变了烟酰胺腺嘌呤二核苷酸磷酸(NADPH)的水平,从而导致氧化应激,并下调 Nrf-2 以抑制胶质母细胞瘤。我们的研究为理解Chr-A的抗胶质瘤机制提供了一个新的视角,凸显了其作为一种有潜力的胶质母细胞瘤化疗药物的潜力。
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Chrysomycin A Reshapes Metabolism and Increases Oxidative Stress to Hinder Glioblastoma Progression
Glioblastoma represents the predominant and a highly aggressive primary neoplasm of the central nervous system that has an abnormal metabolism. Our previous study showed that chrysomycin A (Chr-A) curbed glioblastoma progression in vitro and in vivo. However, whether Chr-A could inhibit orthotopic glioblastoma and how it reshapes metabolism are still unclear. In this study, Chr-A markedly suppressed the development of intracranial U87 gliomas. The results from airflow-assisted desorption electrospray ionization mass spectrometry imaging (AFADESI-MSI) indicated that Chr-A improved the abnormal metabolism of mice with glioblastoma. Key enzymes including glutaminase (GLS), glutamate dehydrogenases 1 (GDH1), hexokinase 2 (HK2) and glucose-6-phosphate dehydrogenase (G6PD) were regulated by Chr-A. Chr-A further altered the level of nicotinamide adenine dinucleotide phosphate (NADPH), thus causing oxidative stress with the downregulation of Nrf-2 to inhibit glioblastoma. Our study offers a novel perspective for comprehending the anti-glioma mechanism of Chr-A, highlighting its potential as a promising chemotherapeutic agent for glioblastoma.
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来源期刊
Marine Drugs
Marine Drugs 医学-医药化学
CiteScore
9.60
自引率
14.80%
发文量
671
审稿时长
1 months
期刊介绍: Marine Drugs (ISSN 1660-3397) publishes reviews, regular research papers and short notes on the research, development and production of drugs from the sea. Our aim is to encourage scientists to publish their experimental and theoretical research in as much detail as possible, particularly synthetic procedures and characterization information for bioactive compounds. There is no restriction on the length of the experimental section.
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