Department of Biochemistry, Faculty of Pharmacy, Duzce University, Duzce, Turkey.
Department of Medical Biochemistry, Faculty of Medicine, Duzce University, Duzce, Turkey.
Environ Toxicol. 2023 Jul;38(7):1690-1701. doi: 10.1002/tox.23797. Epub 2023 Mar 29.
Glioblastoma (GBM) is classified as a stage-IV glioma. Unfortunately, there are currently no curative treatments for GBM. Poly(rC)-binding protein 1 (PCBP1) is a cytosolic iron chaperone with diverse functions. PCBP1 is also known to regulate autophagy, but the role of PCBP1 in ferroptosis, iron-dependent cell death pathway, remains unrevealed in GBM cells. Here, we investigated the effects of borax, a boron compound, on the ferroptosis signaling pathway mediated by PCBP1 and autophagy. The study analyzed cell viability, proliferation, and cell cycle on U87-MG and HMC3 cells to investigate the effects of borax. After determining the cytotoxic concentrations of borax, morphological analyzes and measurement of PCBP1, Beclin1, malondialdehyde (MDA), glutathione (GSH), glutathione peroxidase 4 (GPx4) and acyl-CoA synthetase long chain family member 4 (ACSL4) levels were performed. Finally, expression levels of PCBP1, Beclin1, GPx4 and ACSL4, and caspase-3/7 activity were determined. We found that borax reduced U87-MG cell viability in a concentration- and time-dependent manner. Additionally, borax altered cell proliferation and remarkably reduced S phase in the U87-MG cells and exhibited selectivity by having an opposite effect on normal cells (HMC3). According to DAPI staining, borax caused nuclear deficits in U87-MG cells. The result showed that borax in U87-MG cells induced reduction of the PCBP1, GSH, and GPx4 and enhancement of Beclin1, MDA, and ACSL4. Furthermore, borax triggered apoptosis by activating caspase 3/7 in U87-MG cells. Our study indicated that the borax has potential as an anticancer treatment for GBM via regulating PCBP1/Beclin1/GPx4/ACSL4 signaling pathways.
胶质母细胞瘤（GBM）被归类为 IV 期神经胶质瘤。不幸的是，目前没有治愈 GBM 的方法。聚（C）结合蛋白 1（PCBP1）是一种具有多种功能的细胞质铁伴侣蛋白。PCBP1 还已知调节自噬，但在 GBM 细胞中，PCBP1 在铁依赖性细胞死亡途径铁死亡中的作用尚未揭示。在这里，我们研究了硼砂（一种硼化合物）对 PCBP1 和自噬介导的铁死亡信号通路的影响。该研究分析了 U87-MG 和 HMC3 细胞的细胞活力、增殖和细胞周期，以研究硼砂的作用。确定硼砂的细胞毒性浓度后，进行形态分析和 PCBP1、Beclin1、丙二醛（MDA）、谷胱甘肽（GSH）、谷胱甘肽过氧化物酶 4（GPx4）和长链酰基辅酶 A 合成酶家族成员 4（ACSL4）水平的测量。最后，测定了 PCBP1、Beclin1、GPx4 和 ACSL4 的表达水平以及 caspase-3/7 的活性。我们发现硼砂以浓度和时间依赖的方式降低 U87-MG 细胞活力。此外，硼砂改变了细胞增殖，并且在 U87-MG 细胞中明显降低 S 期，并对正常细胞（HMC3）表现出选择性。根据 DAPI 染色，硼砂导致 U87-MG 细胞的核缺陷。结果表明，硼砂在 U87-MG 细胞中诱导 PCBP1、GSH 和 GPx4 减少，Beclin1、MDA 和 ACSL4 增加。此外，硼砂通过激活 U87-MG 细胞中的 caspase 3/7 诱导细胞凋亡。我们的研究表明，硼砂通过调节 PCBP1/Beclin1/GPx4/ACSL4 信号通路具有作为 GBM 抗癌治疗的潜力。
