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白蛋白-绿原酸纳米颗粒对MDA-MB-435s细胞凋亡及PI3K/Akt/mTOR信号通路抑制活性的影响

Effects of Albumin-Chlorogenic Acid Nanoparticles on Apoptosis and PI3K/Akt/mTOR Pathway Inhibitory Activity in MDA-MB-435s Cells.

作者信息

Alzahrani Badr, Elderdery Abozer Y, Alsrhani Abdullah, Alzerwi Nasser A N, Althobiti Maryam Musleh, Rayzah Musaed, Idrees Bandar, Elkhalifa Ahmed M E, Subbiah Suresh K, Mok Pooi Ling

机构信息

Department of Clinical Laboratory Sciences, College of Applied Medical Sciences, Jouf University, Sakaka 72388, Saudi Arabia.

Department of Surgery, College of Medicine, Majmaah University, P.O. Box 66, Al-Majmaah 11952, Saudi Arabia.

出版信息

Nanomaterials (Basel). 2023 Apr 22;13(9):1438. doi: 10.3390/nano13091438.

Abstract

In this study, we synthesized, characterized, and explored the anti-microbial and anti-cancer effects of albumin-chlorogenic acid nanoparticles (NPs). Characterization studies with a UV-vis spectrophotometer, FTIR, PL spectrum, TEM, FESEM, XRD, and DLA analysis showed patterns confirming the physio-chemical nature of biogenic nanocomposites. Further, anti-microbial studies using bacterial strains , , , , , , and fungal strain showed significant ( < 0.05) anti-bacterial and anti-fungal activities. Next, we used MDA-MB-435s, a human cell line, to evaluate the anti-cancer effects of albumin-chlorogenic acid NPs. Cytotoxic studies revealed its IC50 concentration at 24 μg/mL after a 24 h treatment of MDA-MB-435s cells. We chose this IC50 dose to analyze albumin-chlorogenic acid NPs anti-cancer effects in vitro. MDA-MB-435s cells exposed to our NPs were studied via AO/EtBr staining, cell cycle analyses via PI staining, the status of whole genomic damage via comet assay, levels of apoptotic cells via annexin V/PI staining, ROS generation via DCFH-DA staining, an assay of antioxidant enzymes catalase, superoxide dismutase, and antioxidant GSH, via ELISA analyses of apoptotic markers caspase-3, 8, 9, Bax, Bcl-2, CytC, and p53, PI3/AKT/mTOR pathway. Our results collectively showed albumin-chlorogenic acid NPs induced apoptosis via p53-dependent and PI3/AKT/mTOR inhibition in MDA-MB-435s cells. Our results denote albumin-chlorogenic acid NPs can be used as an effective candidate for anti-microbial and anti-cancer applications; however, further in vivo confirmatory studies are warranted.

摘要

在本研究中,我们合成、表征并探究了白蛋白 - 绿原酸纳米颗粒(NPs)的抗菌和抗癌作用。使用紫外可见分光光度计、傅里叶变换红外光谱仪、光致发光光谱、透射电子显微镜、场发射扫描电子显微镜、X射线衍射和动态光散射分析进行的表征研究显示出证实生物源纳米复合材料物理化学性质的模式。此外,使用细菌菌株、、、、、、和真菌菌株进行的抗菌研究显示出显著的(<0.05)抗菌和抗真菌活性。接下来,我们使用人细胞系MDA - MB - 435s来评估白蛋白 - 绿原酸纳米颗粒的抗癌作用。细胞毒性研究显示,在对MDA - MB - 435s细胞进行24小时处理后,其IC50浓度为24μg/mL。我们选择这个IC50剂量来分析白蛋白 - 绿原酸纳米颗粒在体外的抗癌作用。通过AO/EtBr染色、PI染色进行细胞周期分析、彗星试验检测全基因组损伤状态、annexin V/PI染色检测凋亡细胞水平、DCFH - DA染色检测活性氧生成、通过ELISA分析凋亡标志物caspase - 3、8、9、Bax、Bcl - 2、CytC和p53、PI3/AKT/mTOR途径,对暴露于我们纳米颗粒的MDA - MB - 435s细胞进行了研究。我们的结果共同表明,白蛋白 - 绿原酸纳米颗粒通过p53依赖性和PI3/AKT/mTOR抑制在MDA - MB - 435s细胞中诱导凋亡。我们的结果表明,白蛋白 - 绿原酸纳米颗粒可作为抗菌和抗癌应用的有效候选物;然而,有必要进行进一步的体内验证研究。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8f56/10180018/14a40cceef36/nanomaterials-13-01438-g001.jpg

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