scholarly journals Cell Matrix Remodeling Ability Shown by Image Spatial Correlation

2013 ◽  
Vol 2013 ◽  
pp. 1-8 ◽  
Author(s):  
Chi-Li Chiu ◽  
Michelle A. Digman ◽  
Enrico Gratton

Extracellular matrix (ECM) remodeling is a critical step of many biological and pathological processes. However, most of the studies to date lack a quantitative method to measure ECM remodeling at a scale comparable to cell size. Here, we applied image spatial correlation to collagen second harmonic generation (SHG) images to quantitatively evaluate the degree of collagen remodeling by cells. We propose a simple statistical method based on spatial correlation functions to determine the size of high collagen density area around cells. We applied our method to measure collagen remodeling by two breast cancer cell lines (MDA-MB-231 and MCF-7), which display different degrees of invasiveness, and a fibroblast cell line (NIH/3T3). We found distinct collagen compaction levels of these three cell lines by applying the spatial correlation method, indicating different collagen remodeling ability. Furthermore, we quantitatively measured the effect of Latrunculin B and Marimastat on MDA-MB-231 cell line collagen remodeling ability and showed that significant collagen compaction level decreases with these treatments.

2017 ◽  
Vol 63 (1) ◽  
pp. 141-145
Author(s):  
Yuliya Khochenkova ◽  
Eliso Solomko ◽  
Oksana Ryabaya ◽  
Yevgeniya Stepanova ◽  
Dmitriy Khochenkov

The discovery for effective combinations of anticancer drugs for treatment for breast cancer is the actual problem in the experimental chemotherapy. In this paper we conducted a study of antitumor effect of the combination of sunitinib and bortezomib against MDA-MB-231 and SKBR-3 breast cancer cell lines in vitro. We found that bortezomib in non-toxic concentrations can potentiate the antitumor activity of sunitinib. MDA-MB-231 cell line has showed great sensitivity to the combination of bortezomib and sunitinib in vitro. Bortezomib and sunitinib caused reduced expression of receptor tyrosine kinases VEGFR1, VEGFR2, PDGFRa, PDGFRß and c-Kit on HER2- and HER2+ breast cancer cell lines


2018 ◽  
Vol 18 (2) ◽  
pp. 295-301 ◽  
Author(s):  
Shabnam Farzaneh ◽  
Elnaz Zeinalzadeh ◽  
Bahram Daraei ◽  
Soraya Shahhosseini ◽  
Afshin Zarghi

Background: Due to the astonishing properties of ferrocene and its derivatives, it has a broad application in diverse areas. Numerous ferrocene derivatives demonstrated anti-proliferative activity. Also COX-2, as a key isoenzyme for production of prostaglandins, is frequently overexpressed in various cancers. It is now recognized that COX-2 over expression promotes tumorigenic functions which can be suppressed by COX-2 inhibitors, a phenomenon useful for the preventing of tumor progression. The combination of COX-2 inhibitors with other anti-cancer or cancer prevention drugs may reduce their side effects in future cancer prevention and treatment. Objective: Owing to high anticancer potential of ferrocene derivatives and considerable COX-2 inhibitory and cytotoxicity effects of our previously synthesized chalcones, we decided to incorporate the ferrocenyl moiety into appropriate COX-2 inhibitor chalcone based scaffold, to evaluate COX-2 inhibitory activity as well as anticancer activities. Methods: Chalcones were synthesized via clasien-schmidt condensation of methylsulfonyl aldehyde and acetyl ferrocene. Further different amines with solvent free and ultra sound condition were reacted with chalcones to have different 1-ferrocenyl-3-amino carbonyl compounds. Docking study was carried out with Auto Dock vina software. All the newly-synthesized compounds were evaluated for their cyclooxygenase-2 (COX-2) inhibitory activity using chemiluminescent enzyme assays as well as cytotoxicity activity against MCF-7 and T47D and fibroblast cell lines by MTT assay. Results: In vitro COX-1/COX-2 inhibition studies demonstrated that all compounds were selective inhibitors of the COX-2 isozyme with IC50 values in the highly potent 0.05-0.12 µM range, and COX-2 selectivity indexes (SI) in the 148.3-313.7 range. These results indicated that either potency or selectivity of COX-2 inhibitory activity was affected by the nature and size of the substituents on C-3 of propane-1-one. Also anti-proliferative and toxicity activities of synthesized compounds against breast cancer cell lines MCF-7 and T47D and fibroblast cell lines showed that the synthesized compounds had mild to moderate cytotoxicity against MCT7 and T47D breast cancer cell lines at 10 µM concentration. In vitro COX-1/COX-2 inhibition studies and anticancer activity against MCF-7, identified 1-ferrocenyl-3-(4-methylsulfonylphenyl) propen-1-one as a potent compound (IC50 COX-2 = 0.05 µM, MCF-7: % inhibition (at concentration of 10 µM) = 32.7%), and also 1-ferrocenyl-3- (propan-1-amine)-3-(4-methylsulfonylphenyl) propan-1-one showed the most selectivity on COX-2 inhibition (selectivity index= 313.7). Conclusion: A novel group of ferrocene compounds, possessing a methyl sulfonyl COX-2 pharmacophore were synthesized to investigate the effect of different substituents on selectivity and potency of COX-2 inhibitory activity and their cytotoxicity effects. This study indicates that 1-ferrocenyl-3-amino carbonyl compounds having ferrocene motif and methyl sulfonyl COX-2 pharmacophore is a suitable scaffold to design COX-2 inhibitors and anti-cancer agents.


Nanomaterials ◽  
2021 ◽  
Vol 11 (5) ◽  
pp. 1183
Author(s):  
Cecilia Spedalieri ◽  
Gergo Péter Szekeres ◽  
Stephan Werner ◽  
Peter Guttmann ◽  
Janina Kneipp

Gold nanostars are a versatile plasmonic nanomaterial with many applications in bioanalysis. Their interactions with animal cells of three different cell lines are studied here at the molecular and ultrastructural level at an early stage of endolysosomal processing. Using the gold nanostars themselves as substrate for surface-enhanced Raman scattering, their protein corona and the molecules in the endolysosomal environment were characterized. Localization, morphology, and size of the nanostar aggregates in the endolysosomal compartment of the cells were probed by cryo soft-X-ray nanotomography. The processing of the nanostars by macrophages of cell line J774 differed greatly from that in the fibroblast cell line 3T3 and in the epithelial cell line HCT-116, and the structure and composition of the biomolecular corona was found to resemble that of spherical gold nanoparticles in the same cells. Data obtained with gold nanostars of varied morphology indicate that the biomolecular interactions at the surface in vivo are influenced by the spike length, with increased interaction with hydrophobic groups of proteins and lipids for longer spike lengths, and independent of the cell line. The results will support optimized nanostar synthesis and delivery for sensing, imaging, and theranostics.


1993 ◽  
Vol 21 (2) ◽  
pp. 206-209
Author(s):  
Anders H. G. Andrén ◽  
Anders P. Wieslander

Cytotoxicity, measured as inhibition of cell growth of cultured cell lines, is a widely used method for testing the safety of biomaterials and chemicals. One major technical disadvantage with this method is the continuous routine maintenance of the cell lines. We decided to investigate the possibility of storing stock cultures of fibroblasts (L-929) in an ordinary refrigerator as a means of reducing the routine workload. Stock cultures of the mouse fibroblast cell line L-929 were prepared in plastic vials with Eagle's minimum essential medium. The vials were stored in a refrigerator at 4–10°C for periods of 7–31 days. The condition of the cells after storage was determined as cell viability, cell growth and the toxic response to acrylamide, measured as cell growth inhibition. We found that the L-929 cell line can be stored for 2–3, weeks with a viabilty > 90% and a cell growth of about 95%, compared to L-929 cells grown and subcultured in the normal manner. The results also show that the toxic response to acrylamide, using refrigerator stored L-929 cells, corresponds to that of control L-929 cells. We concluded that it is possible to store L-929 cells in a refrigerator for periods of up to 3 weeks and still use the cells for in vitro cytotoxic assays.


1986 ◽  
Vol 103 (6) ◽  
pp. 2411-2420 ◽  
Author(s):  
E F Plow ◽  
D E Freaney ◽  
J Plescia ◽  
L A Miles

The capacity of cells to interact with the plasminogen activator, urokinase, and the zymogen, plasminogen, was assessed using the promyeloid leukemic U937 cell line and the diploid fetal lung GM1380 fibroblast cell line. Urokinase bound to both cell lines in a time-dependent, specific, and saturable manner (Kd = 0.8-2.0 nM). An active catalytic site was not required for urokinase binding to the cells, and 55,000-mol-wt urokinase was selectively recognized. Plasminogen also bound to the two cell lines in a specific and saturable manner. This interaction occurred with a Kd of 0.8-0.9 microM and was of very high capacity (1.6-3.1 X 10(7) molecules bound/cell). The interaction of plasminogen with both cell types was partially sensitive to trypsinization of the cells and required an unoccupied high affinity lysine-binding site in the ligand. When plasminogen was added to the GM1380 cells, a line with high intrinsic plasminogen activator activity, the bound ligand was comprised of both plasminogen and plasmin. Urokinase, in catalytically active or inactive form, enhanced plasminogen binding to the two cell lines by 1.4-3.3-fold. Plasmin was the predominant form of the bound ligand when active urokinase was added, and preformed plasmin can also bind directly to the cells. Plasmin on the cell surface was also protected from its primary inhibitor, alpha 2-antiplasmin. These results indicate that the two cell lines possess specific binding sites for plasminogen and urokinase, and a family of widely distributed cellular receptors for these components may be considered. Endogenous or exogenous plasminogen activators can generate plasmin on cell surfaces, and such activation may provide a mechanism for arming cell surfaces with the broad proteolytic activity of this enzyme.


2017 ◽  
Vol 2017 ◽  
pp. 1-10 ◽  
Author(s):  
Vincenza Barresi ◽  
Carmela Bonaccorso ◽  
Domenico A. Cristaldi ◽  
Maria N. Modica ◽  
Nicolò Musso ◽  
...  

Recent drug discovery efforts are highly focused towards identification, design, and synthesis of small molecules as anticancer agents. With this aim, we recently designed and synthesized novel compounds with high efficacy and specificity for the treatment of breast tumors. Based on the obtained results, we constructed a Volsurf+ (VS+) model using a dataset of 59 compounds able to predict the in vitro antitumor activity against MCF-7 cancer cell line for new derivatives. In the present paper, in order to further verify the robustness of this model, we report the results of the projection of more than 150 known molecules and 9 newly synthesized compounds. We predict their activity versus MCF-7 cell line and experimentally verify the in silico results for some promising chosen molecules in two human breast cell lines, MCF-7 and MDA-MB-231.


2013 ◽  
Vol 64 (2) ◽  
Author(s):  
Siti Nur Atiqah Md Othman ◽  
Norazah Basar ◽  
Siti Pauliena Mohd Bohari

P. macrocarpa is a well known Indonesian medicinal plant which is traditionally claimed to have anticancer properties. To date, there are numerous cytotoxic studies conducted on crude extracts of this plant. However, there are limited informations available regarding cytotoxic activity of the compounds isolated from this plant. Thus, this study investigated cytotoxic activity of two benzophenones derivatives identified as 2,6,4'-trihydroxy-4-methoxybenzophenone (1) and 6,4'-dihydroxy-4-methoxybenzophenone-2-O-β-D-glucopyranoside (2) isolated from the ethyl acetate extract. Cytotoxic activities of these compounds were performed against human cervical carcinoma cell line (HeLa) and mouse embryonic fibroblast cell line (3T3) using MTT assay. The result showed that benzophenone (1)  exhibited low cytotoxic effect against HeLa and 3T3 cell lines with IC50 values of 132 µg/ml and 158 µg/ml, repectively while benzophenone (2) was non toxic against HeLa and 3T3 cell lines are because the IC50 is more than 250 µg/ml. These findings may sheds light on the actual properties of this plant.


2016 ◽  
Vol 63 (3) ◽  
Author(s):  
Karolina Kowalska ◽  
Magdalena Nowakowska ◽  
Kamila Domińska ◽  
Agnieszka W. Piastowska-Ciesielska

The aim of this study was to evaluate the coexpression of caveolin-1 (CAV-1), angiotensin II type 1 receptor (AT1-R) and forkhead box Ml (FOXM1) in prostate and breast cancer cell lines, in comparison with normal cell lines. CAV-1, AT1-R and FOXM1 expression was determined by reverse transcription-quantitative polymerase chain reaction and western blot analysis in the prostate cancer cell lines PC3, DU145 and LNCaP; prostate normal cell line PNT1A; breast cancer cell lines MCF-7 and MDA-MB-231; and the normal breast cell line 184A1. A correlation between the expression levels of the investigated genes and their metastatic properties was determined by the Spearman's rank test (P<0.05) and Aspin-Welsch t-test, respectively. In prostate cell lines, a significant correlation was noted between CAV-1 and AT1-R expression and between FOXM1 and CAV-1 expression. A correlation between the expression levels of the investigated genes and their metastatic potential was also observed, with relatively high expression of all the investigated genes in the normal prostate cell line PNT1A. In comparison to prostate cancer cell lines, an adverse dependency between CAV-1, AT1-R, FOXM1 expression and metastatic potential was observed in the breast cancer cell lines. Relatively high expression of all tested genes was observed in the normal breast cell line 184A1, which was decreasing respectively with increasing metastatic potential of breast cancer cell lines. The results obtained here indicate that CAV-1, FOXM1 and AT1-R may be potential markers of tumorigenesis in certain types of cancer in vitro.


2020 ◽  
Author(s):  
Adriane Feijo Evangelista ◽  
Renato J Oliveira ◽  
Viviane A O Silva ◽  
Rene A D C Vieira ◽  
Rui M Reis ◽  
...  

Abstract Introduction: Breast cancer is the most frequently diagnosed malignancy among women. However, the role of microRNA expression in breast cancer progression is not fully understood. In this study we examined predictive interactions between differentially expressed miRNAs and mRNAs in breast cancer cell lines representative of the common molecular subtypes. Integrative bioinformatics analysis identified miR-193 and miR-210 as potential regulatory biomarkers of mRNA in breast cancer. Several recent studies have investigated these miRNAs in a broad range of tumors, but the mechanism of their involvement in cancer progression has not previously been investigated. Methods: The miRNA-mRNA interactions in breast cancer cell lines were identified by parallel expression analysis and miRNA target prediction programs. The expression profiles of mRNA and miRNAs from luminal (MCF-7, MCF-7/AZ and T47D), HER2 (BT20 and SK-BR3) and triple negative subtypes (Hs578T e MDA-MB-231) could be clearly separated by unsupervised analysis using HB4A cell line as a control. Breast cancer miRNA data from TCGA patients were grouped according to molecular subtypes and then used to validate these findings. Expression of miR-193 and miR-210 was investigated by miRNA transient silencing assays using the MCF7, BT20 and MDA-MB-231 cell lines. Functional studies included, xCELLigence system, ApoTox-Glo triplex, flow cytometry and transwell assays were performed to determine cell proliferation, cytotoxicity, apoptosis, migration and invasion, respectively. Results: The most evident effects were associated with cell proliferation after miR-210 silencing in triple negative subtype cell line MDA-MB-231. Using in silico prediction algorithms, TNFRSF10 was identified as one of the potential downstream targets for both miRNAs. The TNFRSF10C and TNFRSF10D mRNA expression inversely correlated with the expression levels of miR-193 and miR210 in breast cell lines and breast cancer patients, respectively. Other potential regulated genes whose expression also inversely correlated with both miRNAs were CCND1, a mediator on invasion and metastasis, and the tumor suppressor gene RUNX3. Conclusion: In summary, our findings identify miR-193 and miR-210 as potential regulatory miRNA in different molecular subtypes of breast cancer and suggest that miR-210 may have specific role in MDA-MB-231 proliferation. Our results highlight important new downstream regulated targets that may serve as promising therapeutic pathways for aggressive breast cancers.


Nutrients ◽  
2020 ◽  
Vol 12 (1) ◽  
pp. 154 ◽  
Author(s):  
Agata Jabłońska-Trypuć ◽  
Urszula Wydro ◽  
Elżbieta Wołejko ◽  
Grzegorz Świderski ◽  
Włodzimierz Lewandowski

Cichoric acid (CA) belongs to the group of polyphenols, which occurs in a variety of plant species and it is characterized by anticancer, antibacterial, and antiviral properties. Selected polyphenols have the ability to combine with metal ions to form chelate complexes that reveal greater biological activity than free compounds. In order to study possible antimicrobial and anticancer effect of CA and its complexes with copper(II)/zinc(II)/nickel(II)/cobalt(II) we decided to conduct cytotoxicity tests to estimate the most effective concentrations of tested compounds. The results of the presented study demonstrated, for the first time, that the treatment with newly synthesized CA-metal complexes has anticancer and antimicrobial effects, which were examined in seven different cell lines: MCF-7, MDA-MB-231, and ZR-75-1 breast cancer cell lines, A375 melanoma cell line, DLD-1 cell line, LN-229 cell line, FN cell line; five bacterial strains: Escherichia coli, Pseudomonas aeruginosa, Staphylococcus epidermidis, Proteus vulgaris, Lactobacillus rhamnosus, yeast Sacchcaromyces boulardii, and pathogenic yeast-like fungi Candida albicans. The presented study indicates that CA-metal complexes could be considered as a potential supplementary tool in anticancer therapy, however, because of their possible toxic activity on fibroblasts, they should be used with caution. Some of the tested complexes have also preservative properties and positive influence on normal non-pathogenic microorganisms, which was demonstrated in selected microbial strains, therefore they may serve as food preservatives of natural origin with cytoprotective properties.


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