Silver Nanoparticles Modulate the Epithelial-to-Mesenchymal Transition in Estrogen-Dependent Breast Cancer Cells In Vitro

Rakowski, Michał; Porębski, Szymon; Grzelak, Agnieszka

doi:10.3390/ijms22179203

Cited by 16 publications

(11 citation statements)

References 87 publications

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“…In a recent study, it has been reported that AgNPs can regulate signaling pathways or can block tumor cell metastasis by inhibiting angiogenesis [ 89 ]. Rakowski et al [ 90 ] demonstrated that AgNPs can modulate the metastasis of MCF-7 breast cancer cells across the EMT pathway and can modify the metabolism of breast cancer cells by inducing reactive oxygen species (ROS) generation. Furthermore, Lee et al [ 91 ] have shown that the anticancer mechanism involves also the down-regulation of the antiapoptotic proteins, such as BCL-2, and upregulation of ROS, caspase 3 and P53 proteins.…”

Section: Discussionmentioning

confidence: 99%

Green Synthesis of Silver Nanoparticles Using Populi gemmae Extract: Preparation, Physicochemical Characterization, Antimicrobial Potential and In Vitro Antiproliferative Assessment

et al. 2022

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Green route is an economic, facile and eco-friendly method, employed for the synthesis of various types of nanoparticles, having it as a starting point biological entity, especially as a plant extract. The present study aims to obtain silver nanoparticles (AgNPs) starting from an ethanolic extract of Populi gemmae (Pg), by adjusting the reaction parameters. The morphological and structural characterization exhibited that both the reaction temperature and the concentration of metal salt, contributes to the obtaining of Pg-AgNPs with adjustable size and shape. The newly synthesized nanoparticles exhibited a good antibacterial activity on Gram-positive bacteria as well as antifungal activity. The in vitro antiproliferative activity of Pg-AgNPs was assessed on two different cancer cell lines (breast cancer cells—MCF7 and lung carcinoma epithelial cells—A549). Results have shown that the green-synthetized Pg-AgNPs_S2 (obtained at 60 °C, using AgNO3 of 5 M) induced a substantial decrease in tumor cell viability in a dose-dependent manner with an IC50 ranging from 5.03 to 5.07 µg/mL on A549 cell line and 3.24 to 4.93 µg/mL on MCF7 cell line.

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Section: Discussionmentioning

confidence: 99%

Green Synthesis of Silver Nanoparticles Using Populi gemmae Extract: Preparation, Physicochemical Characterization, Antimicrobial Potential and In Vitro Antiproliferative Assessment

et al. 2022

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“…The role of ROS in the activation of EMT, through HIF1α stabilization, is still unclear, despite the involvement of ROS and HIF-1α in this process which has been highlighted by a number of authors [ 40 , 41 , 42 ]. This evidence was also supported by data showing that antioxidants, such as SkQR1, NAC, Mito-CP, and Mito-TEMPO, are able to modulate EMT [ 41 , 43 , 44 ].…”

Section: Discussionmentioning

confidence: 52%

“…A number of authors have reported the effect of antioxidants, such as SkQR1, NAC, Mito-CP, and Mito-TEMPO [ 41 , 43 , 44 ] on the redox modulation of EMT; however, the involvement of the mitochondrial Complex III UQCRB site in the EMT reversion, due to the inhibition of the hypoxia-induced mitochondrial ROS production and the related decrease in HIF-1α stabilization, represents the novelty of this work and might provide a rationale for the development of drugs able to counteract tumor progression induced by the EMT by blocking mitochondrial ROS production at this site.…”

Section: Discussionmentioning

confidence: 99%

Targeting Mitochondrial ROS Production to Reverse the Epithelial-Mesenchymal Transition in Breast Cancer Cells

Monti

Mancini

Marras

et al. 2022

CIMB

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Experimental evidence implicates reactive oxygen species (ROS) generation in the hypoxic stabilization of hypoxia-inducible factor (HIF)-1α and in the subsequent expression of promoters of tumor invasiveness and metastatic spread. However, the role played by mitochondrial ROS in hypoxia-induced Epithelial-Mesenchymal Transition (EMT) activation is still unclear. This study was aimed at testing the hypothesis that the inhibition of hypoxia-induced mitochondrial ROS production, mainly at the mitochondrial Complex III UQCRB site, could result in the reversion of EMT, in addition to decreased HIF-1α stabilization. The role of hypoxia-induced ROS increase in HIF-1α stabilization and the ability of antioxidants, some of which directly targeting mitochondrial Complex III, to block ROS production and HIF-1α stabilization and prevent changes in EMT markers were assessed by evaluating ROS, HIF-1α and EMT markers on breast cancer cells, following 48 h treatment with the antioxidants. The specific role of UQCRB in hypoxia-induced EMT was also evaluated by silencing its expression through RNA interference and by assessing the effects of its downregulation on ROS production, HIF-1α levels, and EMT markers. Our results confirm the pivotal role of UQCRB in hypoxic signaling inducing EMT. Thus, UQCRB might be a new therapeutic target for the development of drugs able to reverse EMT by blocking mitochondrial ROS production.

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“… 49 The specificities and function are dictated by the biochemical properties of the structure and their functional groups. Standard AgNPs are known to have cytotoxic properties in vitro, 50 but with green synthesis, therapeutic secondary plant metabolites surrounding the silver nucleus can lead to additional properties 51 and possibly a targeted approach that leads to selectivity towards certain types of diseased cells, broadening the safety index and the therapeutic implications of the treatment possibly contributing to precision medicine. Thus, it is reasonable to assume that it is the functional groups present in the secondary metabolites surrounding the NPs that dictate the cytotoxic activity, selectivity, and safety profile.…”

Section: Discussionmentioning

confidence: 99%

In silico Prediction of Malvaviscus arboreus Metabolites and Green Synthesis of Silver Nanoparticles – Opportunities for Safer Anti-Bacterial and Anti-Cancer Precision Medicine

Mohammed¹,

Alghamdi²,

Shami³

et al. 2023

IJN

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Biogenic silver nanoparticles (AgNPs) may be a feasible therapeutic option in the research and development towards selectively targeting specific cancers and microbial infections, lending a role in precision medicine. In-silico methods are a viable strategy to aid in drug discovery by identifying lead plant bioactive molecules for further wet lab and animal experiments. Methods: Green synthesis of M-AgNPs was performed using the aqueous extract from the Malvaviscus arboreus leaves, characterized using UV spectroscopy, FTIR, TEM, DLS, and EDS. In addition, Ampicillin conjugated M-AgNPs were also synthesized. The cytotoxic potential of the M-AgNPs was evaluated using the MTT assay on MDA-MB 231, MCF10A, and HCT116 cancer cell lines. The antimicrobial effects were determined using the agar well diffusion assay on methicillin-resistant S. aureus (MRSA) and S. mutans, E. coli, and Klebsiella pneumoniae. Additionally, LC-MS was used to identify the phytometabolites, and in silico techniques were applied to determine the pharmacodynamic and pharmacokinetic profiles of the identified metabolites. Results: Spherical M-AgNPs were successfully biosynthesized with a mean diameter of 21.8 nm and were active on all tested bacteria. Conjugation with ampicillin increased the susceptibility of the bacteria. These antibacterial effects were most predominant in Staphylococcus aureus (p < 0.0001). M-AgNPs had potent cytotoxic activity against the colon cancer cell line (IC 50 =29.5 μg/mL). In addition, four secondary metabolites were identified, Astragalin, 4-hydroxyphenyl acetic acid, Caffeic acid, and Vernolic acid. In silico studies identified Astragalin as the most active antibacterial and anti-cancer metabolite, binding strongly to the carbonic anhydrase IX enzyme with a comparatively higher number of residual interactions. Discussion: Synthesis of green AgNPs presents a new opportunity in the field of precision medicine, the concept centered on the biochemical properties and biological effects of the functional groups present in the plant metabolites used for reduction and capping. M-AgNPs may be useful in treating colon carcinoma and MRSA infections. Astragalin appears to be the optimal and safe lead for further anti-cancer and anti-microbial drug development.

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Silver Nanoparticles Modulate the Epithelial-to-Mesenchymal Transition in Estrogen-Dependent Breast Cancer Cells In Vitro

Cited by 16 publications

References 87 publications

Green Synthesis of Silver Nanoparticles Using Populi gemmae Extract: Preparation, Physicochemical Characterization, Antimicrobial Potential and In Vitro Antiproliferative Assessment

Green Synthesis of Silver Nanoparticles Using Populi gemmae Extract: Preparation, Physicochemical Characterization, Antimicrobial Potential and In Vitro Antiproliferative Assessment

Targeting Mitochondrial ROS Production to Reverse the Epithelial-Mesenchymal Transition in Breast Cancer Cells

In silico Prediction of Malvaviscus arboreus Metabolites and Green Synthesis of Silver Nanoparticles – Opportunities for Safer Anti-Bacterial and Anti-Cancer Precision Medicine

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