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硫代氨基脲与铜纳米颗粒复合物对胃腺癌细胞系(AGS)凋亡的触发作用

Trigger of apoptosis in adenocarcinoma gastric cell line (AGS) by a complex of thiosemicarbazone and copper nanoparticles.

作者信息

Badrooh Mahsa, Shokrollahi Faezeh, Javan Shaghayegh, Ghasemipour Taraneh, Rezaei Mojdehi Samira, Farahnak Haniyeh, Jahani Sayyad Noveiri Mahboubeh, Hedayati Mohammad, Salehzadeh Ali

机构信息

Department of Biology, Rasht Branch, Islamic Azad University, Rasht, Iran.

Department of Medical Sciences, Faculty of Medicine, Sari Branch, Islamic Azad University, Sari, Iran.

出版信息

Mol Biol Rep. 2022 Mar;49(3):2217-2226. doi: 10.1007/s11033-021-07043-z. Epub 2022 Jan 10.

Abstract

BACKGROUND

Seeking novel anticancer agents with minimal side effects against gastric cancer is vitally important. Copper, as an important trace element, takes roles in different physiologic pathways. Also, there is a higher demand for copper in cancer cells than normal ones. Copper complexes containing a therapeutic ligand could be promising candidates for gastric cancer chemotherapy.

METHODS AND RESULTS

In this work, copper oxide nanoparticles were synthesized, functionalized with glutamic acid (CuO@Glu) and conjugated with thiosemicarbazone (CuO@Glu/TSC NPs). The NPs were characterized and their antiproliferative potential against AGS cancer cells was investigated using MTT, flow cytometry, Hoechst staining, and caspase 3 activation assays. The FT-IR results showed the proper binding of TSC to CuO@Glu NPs and crystallinity of the prepared NPs was confirmed by the XRD pattern. The EDX analysis confirmed the presence of Cu, N, C, O, and S elements and lack of impurities. The Hydrodynamic size and zeta potential of the CuO@Glu/TSC NPs were 168 nm and 27.5 mV, respectively. The NPs had spherical shape and were in a size range of 10 to 60 nm in diameter. This work revealed that CuO@Glu/TSC NPs efficiently inhibited the proliferation of AGS cells with significantly lower IC value (203 µg/mL) than normal HEK293 cells (IC = 435 µg/mL). Flow cytometry and Hoechst staining obviously revealed apoptosis induction among CuO@Glu/TSC treated cells, and caspase-3 activity significantly increased by 1.4 folds.

CONCLUSIONS

This study introduced CuO@Glu/TSC as an efficient anticancer against gastric cancer cells with lower toxicity toward normal cells which could be employed for cancer treatment after further studies.

摘要

背景

寻找对胃癌副作用最小的新型抗癌药物至关重要。铜作为一种重要的微量元素,参与不同的生理途径。此外,癌细胞对铜的需求高于正常细胞。含有治疗性配体的铜配合物有望成为胃癌化疗的候选药物。

方法与结果

在本研究中,合成了氧化铜纳米颗粒,用谷氨酸进行功能化修饰(CuO@Glu),并与硫代氨基脲共轭(CuO@Glu/TSC NPs)。对纳米颗粒进行了表征,并使用MTT、流式细胞术、Hoechst染色和caspase 3激活试验研究了它们对AGS癌细胞的抗增殖潜力。傅里叶变换红外光谱(FT-IR)结果表明TSC与CuO@Glu纳米颗粒结合良好,X射线衍射(XRD)图谱证实了所制备纳米颗粒的结晶性。能谱分析(EDX)证实了铜、氮、碳、氧和硫元素的存在且无杂质。CuO@Glu/TSC纳米颗粒的流体动力学尺寸和zeta电位分别为168 nm和27.5 mV。纳米颗粒呈球形,直径在10至60 nm范围内。本研究表明,CuO@Glu/TSC纳米颗粒能有效抑制AGS细胞的增殖,其半数抑制浓度(IC值)为203 μg/mL,明显低于正常HEK293细胞(IC = 435 μg/mL)。流式细胞术和Hoechst染色明显显示CuO@Glu/TSC处理的细胞中诱导了凋亡,caspase-3活性显著增加了1.4倍。

结论

本研究介绍了CuO@Glu/TSC作为一种对胃癌细胞有效的抗癌药物,对正常细胞毒性较低,经进一步研究后可用于癌症治疗。

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