Nosrati Shamim, Javid Hossein, Amiri Hamed, Jafari Niloufar, Hashemy Seyed Isaac
Department of Clinical Biochemistry, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.
Department of Medical Laboratory Sciences, Varastegan Institute for Medical Sciences, Mashhad, Iran.
Naunyn Schmiedebergs Arch Pharmacol. 2025 Feb;398(2):1895-1903. doi: 10.1007/s00210-024-03325-y. Epub 2024 Aug 28.
The significant fatality rate associated with ovarian cancer underscores the urgent need for novel therapeutic interventions in this area. The focus of this study was to assess the cytotoxic impact of auraptene nanohybrid chitosan folate on A2780 ovarian cancer cells. A combination of liquid and solid lipids were used to create auraptene-nanostructured lipid carriers. Folic acid was conjugated to chitosan in order to modify the surface. The nanoparticles containing methylene blue were dissolved in deionized distilled water to attach the chitosan-folic acid to the nanoparticles. The resazurin cell viability assay was employed to gauge the cytotoxicity of auraptene on the cells. Real-time PCR was utilized to quantify the expression levels of Bcl-2, Bax, and P53 genes. DLS analysis exposed a spheroidal particle with an approximate diameter of 211 nm. The auraptene nanoparticles did not revealed inhibitory effect on normal cell line (HFF-1) at the concentrations that it was toxic for cancerous cells (A2780). In vitro trials suggested that auraptene nanoparticles trigger apoptosis in A2780 cells in a dose-responsive manner by promoting the expression of pro-apoptotic genes (Bax and P53), while suppressing the expression of the anti-apoptotic gene (Bcl-2). Furthermore, auraptene nanoparticles also heightened the production of reactive oxygen species within the cancerous cells. The notable cytotoxic and lethal influence of auraptene nanoparticles on human ovarian cancer may be attributed to their capacity to generate oxidative stress conditions and induce apoptosis.
卵巢癌相关的高死亡率凸显了该领域新型治疗干预措施的迫切需求。本研究的重点是评估金雀异黄素纳米杂化壳聚糖叶酸对A2780卵巢癌细胞的细胞毒性作用。使用液体和固体脂质的组合来制备金雀异黄素纳米结构脂质载体。将叶酸与壳聚糖结合以修饰表面。将含有亚甲蓝的纳米颗粒溶解在去离子蒸馏水中,使壳聚糖 - 叶酸附着在纳米颗粒上。采用刃天青细胞活力测定法来评估金雀异黄素对细胞的细胞毒性。利用实时PCR定量Bcl-2、Bax和P53基因的表达水平。动态光散射分析显示出近似直径为211nm的球形颗粒。金雀异黄素纳米颗粒在对癌细胞(A2780)有毒性的浓度下,对正常细胞系(HFF-1)未显示出抑制作用。体外试验表明,金雀异黄素纳米颗粒通过促进促凋亡基因(Bax和P53)的表达,同时抑制抗凋亡基因(Bcl-2)的表达,以剂量响应方式触发A2780细胞凋亡。此外,金雀异黄素纳米颗粒还提高了癌细胞内活性氧的产生。金雀异黄素纳米颗粒对人卵巢癌显著的细胞毒性和致死影响可能归因于它们产生氧化应激条件和诱导凋亡的能力。