scholarly journals Synthesis and Characterization of Green Zinc Oxide Nanoparticles with Antiproliferative Effects through Apoptosis Induction and MicroRNA Modulation in Breast Cancer Cells

2020 ◽  
Vol 2020 ◽  
pp. 1-17
Author(s):  
Amir Hossein Aalami ◽  
Mohammad Mesgari ◽  
Amirhossein Sahebkar

Changes in the expression of microRNAs can affect cancer cells’ viability and behavior and the impact on cancer treatment. In this study, the expression of miR-155-5p, miR-203a-3p, and miR-223-3p in the MCF7 cancer cell line was studied when exposed to ZnO nanoparticles synthesized through a green route. Mentioned ZnO-NPs were well characterized by UV-vis spectroscopy, DLS, XRD, FTIR, FE-SEM, EDX, zeta potential, and AFM analyses. Cellular studies were conducted using ZnO-NPs before miRNA investigations including MTT cytotoxicity test against MCF7, MDA-MB-231, and HFF cell lines. Moreover, apoptosis assays were performed using morphological analysis, fluorescent dyes, flow cytometry, and evaluation of caspase-3 and caspase-8 gene expression. Biological properties such as the antioxidant and antimicrobial activity of these novel ZnO-NPs were considered. MTT assays showed that the inhibitory concentration (IC50) of ZnO-NPs after 24 h was 11.16 μg/mL, 60.08 μg/mL, and 26.3 μg/mL on MCF7, MDA-MB-231, and HFF cells, respectively. The qRT-PCR results showed reduced expression of miR-155-5p, miR-203a-3p, and miR-223-3p when the MCF7 cells were treated with the IC50 concentration of ZnO-NPs (11.16 μg/mL). The antioxidant activity results showed EC50 values at 57.19 μg/mL and 31.5 μg/mL in DPPH and ABTS assays, respectively. The antimicrobial activity of ZnO-NPs was determined on Gram-negative and Gram-positive bacterial strains and fungi using MIC and MBC assays. These NPs had a significant effect in reducing the expression of microRNAs in breast cancer cells. Finally, ZnO-NPs exerted antioxidant and antimicrobial activities.

2017 ◽  
Vol 2017 ◽  
pp. 1-11 ◽  
Author(s):  
Amy L. Strong ◽  
Dorothy T. Pei ◽  
Christian G. Hurst ◽  
Jeffrey M. Gimble ◽  
Matthew E. Burow ◽  
...  

Obesity is associated with enhanced tumor growth and progression. Within the adipose tissue are adipose-derived stromal/stem cells (ASCs) that have been shown to convert into carcinoma-associated fibroblast (CAFs) in the presence of tumor-derived factors. However, the impact of obesity on the ASCs and on the conversion of ASCs into CAFs has not been demonstrated. In the current study, ASCs isolated from lean donors (BMI < 25; lnASCs) were compared with ASCs isolated from obese donors (BMI > 30, obASCs). The contribution of tumor-derived factors on the conversion of ASCs to CAFs was investigated. Following exposure to cancer cells, obASCs expressed higher levels of CAF markers, including NG2, alpha-SMA, VEGF, FAP, and FSP, compared to lnASCs. To investigate the crosstalk between ASCs and breast cancer cells, MCF7 cells were serially cocultured with lnASCs or obASCs. After coculture with lnASCs and obASCs, MCF7 cells demonstrated enhanced proliferation and expressed an invasive phenotype morphologically, with more pronounced effects following exposure to obASCs. Long-term exposure to obASCs also enhanced the expression of protumorgenic factors. Together, these results suggest that obesity alters ASCs to favor their rapid conversion into CAFs, which in turn enhances the proliferative rate, the phenotype, and gene expression profile of breast cancer cells.


2018 ◽  
Vol 16 (2) ◽  
pp. 127-137
Author(s):  
Paula Sofia Coutinho Medeiros ◽  
Ana Lúcia Marques Batista de Carvalho ◽  
Cristina Ruano ◽  
Juan Carlos Otero ◽  
Maria Paula Matos Marques

Background: The impact of the ubiquitous dietary phenolic compound p-coumaric acid on human breast cancer cells was assessed, through a multidisciplinary approach: Combined biological assays for cytotoxicity evaluation and biochemical profiling by Raman microspectroscopic analysis in cells. </P><P> Methods: Para-coumaric acid was shown to exert in vitro chemoprotective and antitumor activities, depending on the concentration and cell line probed: a significant anti-invasive ability was detected for the triple-negative MDA-MB-231 cells, while a high pro-oxidant effect was found for the estrogen- dependent MCF-7 cells. A striking cell selectivity was obtained, with a more noticeable outcome on the triple-negative MDA-MB-231 cell line. Results: The main impact on the cellular biochemical profile was verified to be on proteins and lipids, thus justifying the compound´s anti-invasive effect and chemoprotective ability. Conclusion: p-Coumaric acid was thus shown to be a promising chemoprotective/chemotherapeutic agent, particularly against the low prognosis triple-negative human breast adenocarcinoma.


2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Asrin Pakravan ◽  
Mehdi Azizi ◽  
Fariborz Rahimi ◽  
Farhad Bani ◽  
Farideh Mahmoudzadeh ◽  
...  

Abstract Background Combination chemo-photothermal therapy appears to be one of the next generations of cancer treatment. In this study hollow gold nanostars (HGNSs) and gold nanocages (GNCs) were synthesized and stabilized with thermo-pH-sensitive thiol-end capped ABC triblock copolymer poly(acrylic acid)-b-poly(N isopropylacrylamide)-b-poly (e-caprolactone)-SH; PAA-b-PNIPAAm-b-PCL-SH (GNSs@Pol). Doxorubicin (Dox) was conjugated to the GNSs@Pol nanostructures via ionic interaction, covalent attachment and hydrogen bonding (GNSs@Dox-Pol). The physicochemical characteristics of prepared GNSs@Pol and GNSs were assessed using dynamic light scattering (DLS), transmission electron microscopy (TEM) and zeta potential techniques. Cytocompatibility of the GNSs@Pol was studied by hemolysis assay and MTT assay. The chemo-photothermal therapy (PTT) potential of GNSs@Dox-Pol was compared on MCF7 cells using MTT assay, cell cycle, DAPI staining and Annexin-V apoptosis assay techniques. Results Cell internalization results showed an almost complete uptake of GNSs@Pol by MCF-7 cells in the first 3 h of treatment. The heat generation measurement results showed that both of GNSs have a potential for light to heat conversion (∆T = 23–27 ºC) and HGNSs demonstrated better efficiency than GNCs after 10-min exposure to NIR irradiation. Following chemo-photothermal treatment, the highest cell mortality (90%) and apoptotic effects (97% apoptosis) were observed in HGNSs@Dox-Pol received laser irradiation treatment group. Conclusions This work highlights the potential application of designed GNSs@Dox-Pol in a combinational chemo-PTT to treat breast cancer cells. Graphic abstract


2017 ◽  
Vol 9 (2) ◽  
pp. 103-109
Author(s):  
Rasha Alhaj ◽  
◽  
Alan Purohit ◽  

2021 ◽  
Vol 41 (3) ◽  
pp. 1243-1250
Author(s):  
SLAVOMIR KRAJNAK ◽  
AMELIE LOEWE ◽  
MARCO JOHANNES BATTISTA ◽  
ANNETTE HASENBURG ◽  
ANNE-SOPHIE HEIMES ◽  
...  

Cells ◽  
2020 ◽  
Vol 9 (10) ◽  
pp. 2256
Author(s):  
Konstantina Kyriakopoulou ◽  
Eirini Riti ◽  
Zoi Piperigkou ◽  
Konstantina Koutroumanou Sarri ◽  
Heba Bassiony ◽  
...  

Breast cancer accounts for almost one in four cancer diagnoses in women. Studies in breast cancer patients have identified several molecular markers, indicators of aggressiveness, which help toward more individual therapeutic approaches. In triple-negative breast cancer (TNBC), epidermal growth factor receptor (EGFR) overexpression is associated with increased metastatic potential and worst survival rates. Specifically, abnormal EGFR activation leads to altered matrix metalloproteinases’ (MMPs) expression and, hence, extracellular matrix (ECM) degradation, resulting in induced migration and invasion. The use of matrix substrates for cell culture gives the opportunity to mimic the natural growth conditions of the cells and their microenvironment, as well as cell–cell and cell–matrix interactions. The aim of this study was to evaluate the impact of EGFR inhibition, estrogen receptor beta (ERβ) and different matrix substrates [type I collagen and fibronectin (FN)] on the functional properties, expression of MMPs and cell morphology of ERβ-positive TNBC cells and shERβ ones. Our results highlight EGFR as a crucial regulator of the expression and activity levels of MMPs, while ERβ emerges as a mediator of MMP7 and MT1-MMP expression. In addition, the EGFR/ERβ axis impacts the adhesion and invasion potential of breast cancer cells on collagen type I. Images obtained by scanning electron microscope (SEM) from cultures on the different matrix substrates revealed novel observations regarding various structures of breast cancer cells (filopodia, extravesicles, tunneling nanotubes, etc.). Moreover, the significant contribution of EGFR and ERβ in the morphological characteristics of these cells is also demonstrated, hence highlighting the possibility of dual pharmacological targeting.


2020 ◽  
Vol 8 (1) ◽  
pp. e000195 ◽  
Author(s):  
Johannes Laengle ◽  
Julijan Kabiljo ◽  
Leah Hunter ◽  
Jakob Homola ◽  
Sophie Prodinger ◽  
...  

BackgroundThe monoclonal antibody (mAb) trastuzumab is part of the standard of care for patients with human epidermal growth factor receptor 2 (HER2)-overexpressing breast cancer. Antibody-dependent cell-mediated phagocytosis (ADCP) and cytotoxicity (ADCC) are major mechanisms of action of the mAb trastuzumab. Histone deacetylase inhibitors (HDACi), such as valproic acid (VPA) or vorinostat (SAHA), exert several immunostimulatory properties, which contribute at least in part to their anticancer effect. However, the impact of HDACi-induced immunostimulatory effects on trastuzumab-mediated anti-tumor immune response is not well characterized.MethodsWe analyzed the ADCP and ADCC activity of peripheral blood mononuclear cells (PBMCs) from age and gender-matched healthy volunteers (n=5) against HDACi-treated HER2-overexpressing breast cancer cells (SKBR3), using a well-established in vitro three-color imaging flow cytometry and flow cytometry approach.ResultsVPA and SAHA enhanced trastuzumab-mediated ADCP and trastuzumab-independent cytotoxicity. Mechanistically, VPA upregulated the activating antibody-binding receptor Fc-gamma receptor (FcγR) IIA (CD32A) on monocytes (CD14+). Moreover, VPA and SAHA downregulated the anti-apoptotic protein myeloid leukemia cell differentiation 1 (MCL1) in breast cancer cells. Additionally, VPA and SAHA induced an immunogenic cell death, characterized by the exposure of calreticulin (CALR), as well as decreased the “do not eat me” signal CD47 on tumor cells.ConclusionsHDACi VPA and SAHA increase trastuzumab-mediated phagocytosis and trastuzumab-independent cytotoxicity. The immunomodulatory activities of those HDACi support a rationale combined treatment approach with mAb for cancer treatment.


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