Exploring the potential anti-inflammatory effect of biosynthesized gold nanoparticles using Isodon excisus leaf tissue in human keratinocytes

Dhandapani, Sanjeevram; Wang, Rongbo; Hwang, Ki Cheol; Kim, Hoon; Kim, Yeon-Ju

doi:10.1016/j.arabjc.2023.105113

Cited by 8 publications

(4 citation statements)

References 44 publications

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“…MDA-MB-231 cells were seeded at a density of 5 × 10 5 cells per well and incubated for 24 h. Subsequently, cells were treated with Lys-PP at concentrations of 8.8 and 13.3 μM, as well as cisplatin (cis) at 50 μM. Detailed procedures were carried out as described previously. , A list of antibodies used in this study is listed in Table S5.…”

Section: Experimental Sectionmentioning

confidence: 99%

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Lysine-Rich Polypeptide Modulates Forkhead Box O3 and Phosphoinositide 3-Kinase-Protein Kinase B Pathway To Induce Apoptosis in Breast Cancer

Dhandapani,

Choi,

Chung

et al. 2024

ACS Pharmacol. Transl. Sci.

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The PI3K/AKT/FOXO3 pathway is one of the most frequently involved signaling pathways in cancer, including breast cancer. Therefore, we synthesized a novel lysine-rich polypeptide (Lys-PP) using de novo assembly method and evaluated its anticancer effect. We characterized the structural and physicochemical properties of Lys-PP using various techniques. Later, we used integrated approaches such as in silico, in vitro, and in vivo analysis to confirm the anticancer and therapeutic effect of Lys-PP. First, RNA sequencing suggests Lys-PP disrupted the central carbon metabolic pathway through the modulation of prolactin signaling. Additionally, docking analysis also confirmed the significant association of PI3K/AKT and FOXO3 pathway to induce an apoptotic effect on cancer. Second, Lys-PP exhibited a significant cytotoxicity effect against MDA-MB-231 but no cytotoxic effects on RAW 264.7 and HEK-293, respectively. The cytotoxic effect of Lys-PP-induced apoptosis by an increase in FOXO3a protein expression and a decrease in PI3K/AKT pathway was confirmed by quantitative real-time polymerase chain reaction, immunoblotting, and fluorescent microscopy. Later, immunohistochemistry and hematoxylin and eosin staining on MDA-MD-231 showed increased FOXO3a expression and cell death in the xenograft mice model. Further, liver function, metabolic health, or lipid profile upon Lys-PP showed the absence of significant modulation in the biomarkers except for kidney-related biomarkers. Overall, our comprehensive study provides the first evidence of Lys-PP antibreast cancer action, which could serve as a potential treatment in an alternative or complementary medicine practice.

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Section: Experimental Sectionmentioning

confidence: 99%

“…Detailed procedures were carried out as described previously. 40,41 A list of antibodies used in this study is listed in Table S5. Animal Ethics and Biosafety Statement.…”

Section: ■ Experimental Sectionmentioning

confidence: 99%

Lysine-Rich Polypeptide Modulates Forkhead Box O3 and Phosphoinositide 3-Kinase-Protein Kinase B Pathway To Induce Apoptosis in Breast Cancer

Dhandapani,

Choi,

Chung

et al. 2024

ACS Pharmacol. Transl. Sci.

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“…Gold nanoparticles (GNP) exhibit distinctive optical and physicochemical properties, garnering significant research attention for diverse therapeutic and medical diagnostic applications. , These GNP have proven successful in enhancing the efficacy and specificity of diagnosis and therapy, minimizing side effects in the process . Their potential for improving the effectiveness of various targeted cancer therapies is well-documented .…”

Section: Introductionmentioning

confidence: 99%

Coprisin/Compound K Conjugated Gold Nanoparticles Induced Cell Death through Apoptosis and Ferroptosis Pathway in Adenocarcinoma Gastric Cells

Dhandapani,

Samad,

Liu

et al. 2024

ACS Omega

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Ferroptosis and apoptosis are programmed cell death pathways with distinct characteristics. Sometimes, cancer cells are aided by the induction of a different pathway, such as ferroptosis, when they develop chemoresistance and avoid apoptosis. Identifying the nanomedicine that targets dual pathways is considered as one of the best strategies for diverse cancer types. In our previous work, we synthesized gold nanoparticles (GNP) utilizing Gluconacetobacter liquefaciens in conjunction with compound K (CK) and coprisin (CopA3), yielding GNP-CK-CopA3. Here, we assessed the inhibitory effect of GNP-CK-CopA3 on AGS cells and the induction of apoptosis using Hoechst and PI, Annexin V-FITC/PI, and qRT-PCR. Subsequently, we conducted downstream proteomic analysis and molecular dynamic stimulation to identify the underlying molecular mechanisms. Our investigation of cultured AGS cells treated with varying concentrations of GNP-CK-CopA3 demonstrated the anticancer properties of these nanoparticles. Penetration of GNP-CK-CopA3 into AGS cells was visualized using an enhanced dark field microscope. Apoptosis induction was initially confirmed by treating AGS cells with GNP-CK-CopA3, as evidenced by staining with dyes such as Hoechst and PI. Additionally, mitochondrial disruption and cellular localization induced by GNP-CK-CopA3 were validated through Mito-tracker staining and transmission electron microscopy images. Annexin V-FITC/PI staining was used to distinguish early and late-stage apoptosis or necrosis based on fluorescence patterns. The gene expression of apoptotic markers indicated the initiation of cellular apoptosis. Further, proteomic analysis suggested that the treatment of GNP-CK-CopA3 to AGS cells led to the suppression of 439 proteins and the stimulation of 832 proteins. Among these, ferroptosis emerged as a significant interconnected pathway where glutathione peroxidase 4 (GPX4) and glutathione synthetase (GSS) were significant interacting proteins. Molecular docking and dynamic simulation studies confirmed the binding affinity and stability between CopA3 and CK with GSS and GPX4 proteins, suggesting the role of GNP-CK-CopA3 in ferroptosis induction. Overall, our study showed GNP-CK-CopA3 could play a dual role by inducing apoptosis and ferroptosis to induce AGS cell death.

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“…Studies have shown that GNps are candidates for antioxidant activity, preventing ROS formation, inhibiting free radicals, and increasing antioxidant-active defense enzymes in the body 8 , 9 . The use of GNps in treatment of skin inflammation 14 , 15 , cancer therapy 16 , tumoral vascular leakiness 17 shows the wide application of these nanoparticles in medicine. Therefore, in this study, GNps were used as carriers to transport polyphenols and studied their antioxidant effects on endothelial cells.…”

Section: Introductionmentioning

confidence: 99%

Evaluating the antioxidant potential of resveratrol-gold nanoparticles in preventing oxidative stress in endothelium on a chip

Fayazbakhsh,

Hataminia,

Eslam

et al. 2023

Sci Rep

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Vascular endothelial cells play a vital role in the health and maintenance of vascular homeostasis, but hyperglycemia disrupts their function by increasing cellular oxidative stress. Resveratrol, a plant polyphenol, possesses antioxidant properties that can mitigate oxidative stress. Addressing the challenges of its limited solubility and stability, gold nanoparticles (GNps) were utilized as carriers. A microfluidic chip (MFC) with dynamic flow conditions was designed to simulate body vessels and to investigate the antioxidant properties of resveratrol gold nanoparticles (RGNps), citrate gold nanoparticles (CGNps), and free Resveratrol on human umbilical vein endothelial cells (HUVEC). The 2, 2-diphenyl-1-picrylhydrazyl (DPPH) assay was employed to measure the extracellular antioxidant potential, and cell viability was determined using the Alamar Blue test. For assessing intracellular oxidative stress, the 2′,7′-dichlorodihydrofluorescein diacetate (DCFH-DA) assay was conducted, and results from both the cell culture plate and MFC were compared. Free Resveratrol demonstrated peak DPPH scavenging activity but had a cell viability of about 24–35%. RGNPs, both 3.0 ± 0.5 nm and 20.2 ± 4.7 nm, consistently showed high cell viability (more than about 90%) across tested concentrations. Notably, RGNPs (20 nm) exhibited antioxidative properties through DPPH scavenging activity (%) in the range of approximately 38–86% which was greater than that of CGNps at about 21–32%. In the MFC,the DCFH-DA analysis indicated that RGNPs (20 nm) reduced cellular oxidative stress by 57–82%, surpassing both CGNps and free Resveratrol. Morphologically, cells in the MFC presented superior structure compared to those in traditional cell culture plates, and the induction of hyperglycemia successfully led to the formation of multinucleated variant endothelial cells (MVECs). The MFC provides a distinct advantage in observing cell morphology and inducing endothelial cell dysfunction. RGNps have demonstrated significant potential in alleviating oxidative stress and preventing endothelial cell disorders.

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Exploring the potential anti-inflammatory effect of biosynthesized gold nanoparticles using Isodon excisus leaf tissue in human keratinocytes

Cited by 8 publications

References 44 publications

Lysine-Rich Polypeptide Modulates Forkhead Box O3 and Phosphoinositide 3-Kinase-Protein Kinase B Pathway To Induce Apoptosis in Breast Cancer

Lysine-Rich Polypeptide Modulates Forkhead Box O3 and Phosphoinositide 3-Kinase-Protein Kinase B Pathway To Induce Apoptosis in Breast Cancer

Coprisin/Compound K Conjugated Gold Nanoparticles Induced Cell Death through Apoptosis and Ferroptosis Pathway in Adenocarcinoma Gastric Cells

Evaluating the antioxidant potential of resveratrol-gold nanoparticles in preventing oxidative stress in endothelium on a chip

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