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大戟属银纳米粒子通过下调 PI3Kγ 介导的 PI3K/Akt/mTOR/p70S6K 诱导人肺腺癌细胞 A549 凋亡并发挥抗菌活性。

Silver nanoparticles synthesized by Euphorbia hirta exhibited antibacterial activity and induced apoptosis through downregulation of PI3Kγ mediated PI3K/Akt/mTOR/p70S6K in human lung adenocarcinoma A549 cells.

机构信息

Department of Microbiology, Faculty of Science, Annamalai University, Annamalai Nagar, Chidambaram, India.

出版信息

Environ Toxicol. 2022 Dec;37(12):2865-2876. doi: 10.1002/tox.23643. Epub 2022 Sep 8.

Abstract

Plant extracts were successfully applied to synthesize nanoparticles, and expected such biological processes of effective for chemotherapeutic applications and safe for human use. Our study planned to evaluate the anticancer efficacy of silver nanoparticles (AgNPs) synthesized by Euphorbia hirta on human lung adenocarcinoma A549 cells. The E. hirta synthesized Eh-AgNPs was investigated by UV-spectroscopy, X-ray diffraction, transmission electron microscopy, and Fourier-transform infrared spectroscopy examination. The bactericidal efficacy of Eh-AgNPs was studied by the agar well method, and the cytotoxicity on A549 cells was assessed by MTT assay. Results showed that Eh-AgNPs exhibited effective antibacterial activity against bacterial pathogens, established dose-dependent cytotoxicity on A549 cells, and persuaded apoptosis, as evidenced by increased lipid peroxidation and decreased levels of antioxidants. Eh-AgNPs significantly increased the early apoptosis in A549 cells in a concentration-dependent way. The Eh-AgNPs administration reduced the Bcl-2 expression; however, it increased the expression of p53, Bax, cleaved caspase-3 and -9 apoptotic members. Eh-AgNPs treatment reduced PI3Kγ, phospho-PI3K, phospho-Akt, phospho-mTOR, and p70S6K levels. The obtained results demonstrated that the Eh-AgNPs induce reactive oxygen species-mediated apoptosis by expressing p53, Bax, and inhibiting PI3K/Akt/mTOR/p70S6K signaling pathway.

摘要

植物提取物成功地应用于合成纳米粒子,并期望这些生物过程对化疗应用有效且对人类使用安全。我们的研究计划评估由大戟合成的银纳米粒子(AgNPs)对人肺腺癌细胞 A549 的抗癌功效。通过紫外光谱、X 射线衍射、透射电子显微镜和傅里叶变换红外光谱检查研究了大戟合成的 Eh-AgNPs。通过琼脂孔法研究了 Eh-AgNPs 的杀菌功效,并通过 MTT 测定评估了其对 A549 细胞的细胞毒性。结果表明,Eh-AgNPs 对细菌病原体表现出有效的抗菌活性,对 A549 细胞表现出剂量依赖性细胞毒性,并诱导细胞凋亡,这表现为脂质过氧化增加和抗氧化剂水平降低。Eh-AgNPs 以浓度依赖的方式显著增加 A549 细胞的早期凋亡。Eh-AgNPs 给药减少了 Bcl-2 的表达;然而,它增加了 p53、Bax、cleaved caspase-3 和 -9 凋亡成员的表达。Eh-AgNPs 处理降低了 PI3Kγ、磷酸化 PI3K、磷酸化 Akt、磷酸化 mTOR 和 p70S6K 水平。研究结果表明,Eh-AgNPs 通过表达 p53、Bax 和抑制 PI3K/Akt/mTOR/p70S6K 信号通路,诱导活性氧介导的细胞凋亡。

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