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作为乳腺癌潜在治疗剂的硒纳米颗粒的生物合成:G2/M期阻滞和凋亡诱导。

Biosynthesis of selenium nanoparticles as a potential therapeutic agent in breast cancer: G2/M arrest and apoptosis induction.

作者信息

Ali Basant A, Allam Rasha Mosa, Hasanin Mohamed S, Hassabo Amany A

机构信息

Microbial Chemistry Department, Biotechology Research Institute, National Research Centre, Dokki, Cairo 12622, Egypt.

Pharmacology Department, National Research Centre, Dokki, Cairo 12622, Egypt.

出版信息

Toxicol Rep. 2024 Oct 25;13:101792. doi: 10.1016/j.toxrep.2024.101792. eCollection 2024 Dec.

Abstract

The drawbacks and adverse reactions of conventional breast cancer (BC) medications have prompted researchers to seek novel therapeutic approaches. This study aimed to study the impact of biosynthesized selenium nanoparticles by yeast on breast cancer (MCF-7) cells and to find potential underlying mechanisms. Therefore, marine yeast isolates were screened for their ability to biosynthesis selenium nanoparticles (SeNPs). The most potent isolate was identified as based on 18 S rRNA gene sequencing. Incubation of cell-free extract with 0.8 mM of SeO for 48 h at 40°C in pH of 7.0 were optimal conditions for the biosynthesis of SeNPs. The biosynthesized SeNPs were characterized by UV-Vis spectroscopy, X-ray diffraction (XRD), transmission electron microscopy (TEM), and dynamic light scattering (DLS) measurements including average particle size distribution and average zeta potential. The results showed that the biosynthesized SeNPs displayed a maximum absorbance peak in the UV-Vis spectrum at 560 nm due to surface plasmon resonance. TEM image elevated spherical shape particles with an average size of 12 nm. SRB assay, flow cytometry, and other biochemical methods were employed to assess SeNPs anti-proliferative effects on MCF-7 cells. SeNPs showed superior anticancer efficacy against MCF-7 cells compared to colon (HCT-116) and liver (HepG2) cancer cells, as evidenced by lower IC50 values (19.59 µg/ml) against 36.36 µg/ml and 27.81 ±1.4 µg/ml, respectively. However, SeNPs demonstrated no cytotoxic effects against HSF cells. Moreover, treatment with SeNPs induces G2/M arrest along with triggering apoptosis in MCF-7 cells. Furthermore, MCF-7 cells treated with SeNPs showed increased oxidative stress, as indicated by observable rises in LPO and 8-OHDG, accompanied by considerable exhaustion in antioxidant enzyme activity. These findings demonstrated that Se nanoparticles synthesized from yeast have therapeutic promise in BC treatment.

摘要

传统乳腺癌(BC)药物的缺点和不良反应促使研究人员寻求新的治疗方法。本研究旨在研究酵母生物合成的硒纳米颗粒对乳腺癌(MCF-7)细胞的影响,并找出潜在的作用机制。因此,对海洋酵母分离株进行了筛选,以评估其生物合成硒纳米颗粒(SeNPs)的能力。基于18 S rRNA基因测序,将最有效的分离株鉴定为 。在40°C、pH值为7.0的条件下,将无细胞提取物与0.8 mM的SeO孵育48小时是生物合成SeNPs的最佳条件。通过紫外可见光谱、X射线衍射(XRD)、透射电子显微镜(TEM)和动态光散射(DLS)测量对生物合成的SeNPs进行表征,包括平均粒径分布和平均zeta电位。结果表明,由于表面等离子体共振,生物合成的SeNPs在紫外可见光谱中于560 nm处显示出最大吸收峰。TEM图像显示为平均尺寸为12 nm的球形颗粒。采用SRB测定法、流式细胞术和其他生化方法评估SeNPs对MCF-7细胞的抗增殖作用。与结肠(HCT-116)和肝癌(HepG2)细胞相比,SeNPs对MCF-7细胞显示出更高的抗癌疗效,其对MCF-7细胞的半数抑制浓度(IC50)值较低,分别为19.59 μg/ml,而对结肠癌细胞和肝癌细胞的IC50值分别为36.36 μg/ml和27.81±1.4 μg/ml。然而,SeNPs对人皮肤成纤维细胞(HSF)无细胞毒性作用。此外,SeNPs处理可诱导MCF-7细胞发生G2/M期阻滞并引发细胞凋亡。此外,用SeNPs处理的MCF-7细胞显示氧化应激增加,表现为脂质过氧化(LPO)和8-羟基脱氧鸟苷(8-OHDG)明显升高,同时抗氧化酶活性显著耗尽。这些发现表明,酵母合成的硒纳米颗粒在乳腺癌治疗中具有治疗前景。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/38d0/11565031/6db511db0182/ga1.jpg

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