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硼酸通过SEMA3A/PLXNA1/NRP1信号通路诱导U251胶质母细胞瘤细胞发生氧化损伤和凋亡。

Boric Acid Induces Oxidative Damage and Apoptosis Through SEMA3A/PLXNA1/NRP1 Signalling Pathway in U251 Glioblastoma Cell.

作者信息

Kar Ezgi, Övenler Zeynep, Hacıoğlu Ceyhan, Kar Fatih

机构信息

Department of Nutrition and Dietetics, Faculty of Health Sciences, Kutahya Health Sciences University, Kutahya, Turkey.

Faculty of Medicine, Kutahya Health Sciences University, Kutahya, Turkey.

出版信息

J Cell Mol Med. 2025 May;29(9):e70578. doi: 10.1111/jcmm.70578.

DOI:10.1111/jcmm.70578
PMID:40318008
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12049150/
Abstract

Glioblastoma is one of the deadliest cancers with a very low chance of survival. Glioblastomas have a poor prognosis because of their infiltrative nature, which makes them difficult to totally isolate with rigorous surgery, radiation, and chemotherapy. Our aim in this study was to investigate the efficacy of boric acid, which has anti-cancer properties, on glioblastoma, which has very limited treatment options. U251 human glioblastoma cell lines were treated with IC25 (15.62 μg/mL), IC50 (31.25 μg/mL) and IC75 (62.5 μg/mL) doses of boric acid. Cell viability and proliferation levels were tested. At the same time, the activity of boric acid on cells was tested through oxidative stress, apoptosis, and semaphorin signalling pathway parameters. Our findings indicate that boric acid induced dose-dependent oxidative stress, cellular growth inhibition, apoptosis and morphological changes in U251 cells. Additionally, treatments with increasing amounts of boric acid resulted in a rise in the production of biomarkers of the semaphorin pathway, which may limit cell growth and proliferation. We found that boric acid activates apoptosis by triggering ROS formation at high doses and at the same time inhibits cell proliferation by increasing semaphorin signalling pathway expressions. Boric acid may act as an anti-cancer agent by activating different mechanisms in a dose-dependent manner.

摘要

胶质母细胞瘤是最致命的癌症之一,生存率极低。由于其浸润性,胶质母细胞瘤预后较差,这使得通过严格的手术、放疗和化疗将其完全分离变得困难。我们在本研究中的目的是调查具有抗癌特性的硼酸对治疗选择非常有限的胶质母细胞瘤的疗效。用IC25(15.62μg/mL)、IC50(31.25μg/mL)和IC75(62.5μg/mL)剂量的硼酸处理U251人胶质母细胞瘤细胞系。测试细胞活力和增殖水平。同时,通过氧化应激、细胞凋亡和信号素信号通路参数测试硼酸对细胞的活性。我们的研究结果表明,硼酸在U251细胞中诱导了剂量依赖性的氧化应激、细胞生长抑制、细胞凋亡和形态变化。此外,用越来越多的硼酸处理导致信号素通路生物标志物的产生增加,这可能会限制细胞生长和增殖。我们发现,硼酸通过在高剂量时触发活性氧的形成来激活细胞凋亡,同时通过增加信号素信号通路的表达来抑制细胞增殖。硼酸可能通过以剂量依赖的方式激活不同机制而作为一种抗癌剂发挥作用。

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本文引用的文献

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Boron neutron capture therapy delays the decline in neurological function in a mouse model of metastatic spinal tumors.硼中子俘获治疗延迟转移性脊柱肿瘤小鼠模型中神经功能下降。
Cancer Sci. 2024 Aug;115(8):2774-2785. doi: 10.1111/cas.16245. Epub 2024 Jun 11.
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Borax induces ferroptosis of glioblastoma by targeting HSPA5/NRF2/GPx4/GSH pathways.硼砂通过靶向 HSPA5/NRF2/GPx4/GSH 通路诱导脑胶质瘤发生铁死亡。
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3
Boric Acid Affects Cell Proliferation, Apoptosis, and Oxidative Stress in ALL Cells.
硼酸影响 ALL 细胞的增殖、凋亡和氧化应激。
Biol Trace Elem Res. 2024 Aug;202(8):3614-3622. doi: 10.1007/s12011-023-03958-9. Epub 2023 Nov 28.
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Boron in cancer therapeutics: An overview.硼在癌症治疗中的应用:综述。
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Sema3A Alleviates the Malignant Behaviors of Gastric Cancer Cells by Inhibiting NRP-1.Sema3A 通过抑制 NRP-1 减轻胃癌细胞的恶性行为。
Curr Mol Med. 2024;24(7):931-939. doi: 10.2174/1566524023666230801124826.
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Medicarpin suppresses proliferation and triggeres apoptosis by upregulation of BID, BAX, CASP3, CASP8, and CYCS in glioblastoma.美迪紫檀堿通过上调脑胶质瘤中的 BID、BAX、CASP3、CASP8 和 CYCS 来抑制增殖并引发细胞凋亡。
Chem Biol Drug Des. 2023 Nov;102(5):1097-1109. doi: 10.1111/cbdd.14309. Epub 2023 Jul 28.
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AKR1B1 Represses Glioma Cell Proliferation through p38 MAPK-Mediated Bcl-2/BAX/Caspase-3 Apoptotic Signaling Pathways.醛糖还原酶1B1通过p38丝裂原活化蛋白激酶介导的Bcl-2/BAX/半胱天冬酶-3凋亡信号通路抑制胶质瘤细胞增殖。
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