载杨梅素的藻酸盐-纤维素杂化纳米晶体(MAC-NCs)对人 AGS 胃癌细胞的选择性促凋亡作用。

The selective proapoptotic impact of the myricetin-loaded alginate-cellulose hybrid nanocrystals (MAC-NCs) on the human AGS gastric cancer cells.

机构信息

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

出版信息

Mol Biol Rep. 2024 Sep 19;51(1):998. doi: 10.1007/s11033-024-09864-0.

Abstract

BACKGROUND

Myricetin, a flavanol present in fruits, tea, and vegetables, has the potential to reduce chronic diseases like gastric cancer by promoting cell death and stopping cell growth. However, its limited bioactivity due to its short lifespan and poor solubility in water has been a challenge. The current research focuses on incorporating myricetin into alginate-cellulose hybrid nanocrystals to enhance its selective proapoptotic effects on human AGS gastric cancer cells.

METHODS

MAC-NCs, myricetin-loaded alginate-cellulose hybrid nanocrystals, were synthesized using a combined co-precipitation/ultrasonic homogenization method and characterized through Dynamic Light Scattering (DLS), Fourier Transform Infrared Spectroscopy (FTIR), Field Emission Scanning Electron Microscope (FESEM), and Zeta-potential analyses. Their cytotoxic activity was tested on cancerous (AGS) and normal (Huvec) cells, revealing selective toxicity. Apoptotic markers, Caspase 8 and Caspase 9, gene expression was measured, and cell death type was confirmed using DAPI staining and flow cytometry on AGS cells.

RESULTS

Synthesized MAC-NCs, measuring 40 nm, showed significant selective toxicity on human gastric cells (IC of 31.05 µg/mL) compared to normal endothelial cells (IC of 214.26 µg/mL). DAPI and annexin flow cytometry revealed increased apoptotic bodies in gastric cells, indicating apoptosis. However, the apoptosis was found to be independent of Caspase-8 and Caspase-9.

CONCLUSION

The current study provides critical insights into the therapeutic potential of MAC-NCs for gastric cancer treatment. Based on the notable induction of apoptosis in the AGS cancer cell line, the synthesized MAC-NCs exhibit promising potential as a selective anti-gastric cancer agent. However, further in-vivo studies are necessary to confirm and quantify the nanoparticle's selective toxicity and pharmaceutical properties in future investigations.

摘要

背景

杨梅素是一种存在于水果、茶和蔬菜中的黄烷醇,具有通过促进细胞死亡和阻止细胞生长来减少胃癌等慢性疾病的潜力。然而,由于其半衰期短和在水中的溶解度差,其生物活性有限,这一直是一个挑战。目前的研究集中在将杨梅素纳入海藻酸钠-纤维素混合纳米晶体中,以增强其对人 AGS 胃癌细胞的选择性促凋亡作用。

方法

使用联合共沉淀/超声匀化法合成了负载杨梅素的海藻酸钠-纤维素混合纳米晶体 MAC-NCs,并通过动态光散射(DLS)、傅里叶变换红外光谱(FTIR)、场发射扫描电子显微镜(FESEM)和 Zeta 电位分析对其进行了表征。在癌细胞(AGS)和正常细胞(Huvec)上测试了它们的细胞毒性活性,揭示了选择性毒性。通过 DAPI 染色和流式细胞术在 AGS 细胞上测量了凋亡标记物 Caspase 8 和 Caspase 9 的基因表达,并证实了细胞死亡类型。

结果

合成的 MAC-NCs 粒径为 40nm,对人胃细胞(IC 为 31.05μg/mL)具有显著的选择性毒性,而对正常内皮细胞(IC 为 214.26μg/mL)则没有毒性。DAPI 和膜联蛋白流式细胞术显示胃细胞中凋亡小体增加,表明发生了凋亡。然而,这种凋亡被发现与 Caspase-8 和 Caspase-9 无关。

结论

本研究为 MAC-NCs 治疗胃癌的治疗潜力提供了重要的见解。基于对 AGS 癌细胞系的显著诱导凋亡作用,合成的 MAC-NCs 作为一种选择性抗胃癌药物具有很大的潜力。然而,在未来的研究中,需要进行更多的体内研究来确认和量化纳米颗粒的选择性毒性和药物特性。

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