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水飞蓟素功能化硒纳米颗粒的生物合成及其细胞毒性作用通过下调PI3K/Akt/mTOR通路诱导自噬介导的胃癌细胞凋亡

Biosynthesis and cytotoxic effect of silymarin-functionalized selenium nanoparticles induced autophagy mediated cellular apoptosis via downregulation of PI3K/Akt/mTOR pathway in gastric cancer.

作者信息

Mi Xiao-Jie, Choi Han Sol, Perumalsamy Haribalan, Shanmugam Rajeshkumar, Thangavelu Lakshmi, Balusamy Sri Renukadevi, Kim Yeon-Ju

机构信息

Graduate School of Biotechnology, and College of Life Science, Kyung Hee University, Yongin-si, 17104, Gyeonggi-do, Republic of Korea.

Graduate School of Biotechnology, and College of Life Science, Kyung Hee University, Yongin-si, 17104, Gyeonggi-do, Republic of Korea; Research Institute for Convergence of Basic Science, Hanyang University, Seoul 04763, Republic of Korea.

出版信息

Phytomedicine. 2022 May;99:154014. doi: 10.1016/j.phymed.2022.154014. Epub 2022 Feb 26.

DOI:10.1016/j.phymed.2022.154014
PMID:35247670
Abstract

BACKGROUND

Silymarin, a blend of flavonolignans isolated from plant Silybum marianum L., has long been used as an herbal medicine. Biogenic routes especially the plant-based synthesis of selenium nanoparticles (SeNPs) is safe, eco-friendly, nontoxic and being considered as one of the best strategies for treatment of cancer.

PURPOSE

Silymarin-mediated green synthesis of SeNPs and their possibility as an anticancer agent have not been reported to date. Therefore, our present study was aimed to synthesize and characterize the selenium mediated silymarin nanoparticles (Si-SeNPs) from silymarin and investigate their possibility as an anticancer agent.

METHODS

The physicochemical characteristics of Si-SeNPs were analyzed using various analytical techniques, such as HPLC, field emission-transmission electron microscope, energy-dispersive X-ray spectrometer, and thermogravimetric analysis. The underlying molecular mechanism were evaluated using AGS gastric cancer cells.

RESULTS

Compared with silymarin, the Si-SeNPs exhibited significantly increased cytotoxic effect of AGS cells without exhibiting toxicity on normal cells. Real time PCR and western blotting analysis indicated that Si-SeNPs induced expression of Bax/Bcl-2, cytochrome c, and cleavage of caspase proteins, which is associated with mitochondria-mediated apoptosis signaling in AGS cells. Moreover, agonist assay using PI3K activator indicated that Si-SeNPs-inhibited PI3K/AKT/mTOR pathways were significantly associated as an autophagy and apoptosis signaling in AGS cells.

CONCLUSION

Our study demonstrated the improved anticancer efficacy of Si-SeNPs- induced apoptosis and autophagy pathways, and therefore recommended Si-SeNPs as a novel anticancer agent after in vivo studies.

摘要

背景

水飞蓟素是从植物水飞蓟中分离出的黄酮木脂素混合物,长期以来一直被用作草药。生物合成途径,特别是基于植物的硒纳米颗粒(SeNPs)合成,安全、环保、无毒,被认为是治疗癌症的最佳策略之一。

目的

水飞蓟素介导的SeNPs绿色合成及其作为抗癌剂的可能性迄今尚未见报道。因此,我们目前的研究旨在从水飞蓟素合成并表征硒介导的水飞蓟素纳米颗粒(Si-SeNPs),并研究其作为抗癌剂的可能性。

方法

使用各种分析技术分析Si-SeNPs的物理化学特性,如高效液相色谱、场发射透射电子显微镜、能量色散X射线光谱仪和热重分析。使用AGS胃癌细胞评估潜在的分子机制。

结果

与水飞蓟素相比,Si-SeNPs对AGS细胞的细胞毒性作用显著增加,而对正常细胞无毒性。实时PCR和蛋白质印迹分析表明,Si-SeNPs诱导Bax/Bcl-2、细胞色素c的表达以及半胱天冬酶蛋白的裂解,这与AGS细胞中线粒体介导的凋亡信号有关。此外,使用PI3K激活剂的激动剂试验表明,Si-SeNPs抑制的PI3K/AKT/mTOR途径与AGS细胞中的自噬和凋亡信号显著相关。

结论

我们的研究证明了Si-SeNPs诱导凋亡和自噬途径的抗癌疗效提高,因此建议在体内研究后将Si-SeNPs作为一种新型抗癌剂。

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