scholarly journals Anti-tumor activity of plant extracts against human breast cancer cells are different in monolayer and three-dimensional cell culture screening models: A comparison on 34 extracts

2020 ◽  
Vol 7 (3) ◽  
pp. 3667-3677
Author(s):  
Nhan Lu-Chinh Phan ◽  
Khuong Duy Pham ◽  
Mai Thi-Thanh Nguyen ◽  
Ngoc Kim Phan ◽  
Kiet Dinh Truong ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cell Culture ◽  
Cancer Cells ◽  
Cell Lines ◽  
Plant Extracts ◽  
Breast Cancer Cells ◽  
Three Dimensional ◽  
Culture Model ◽  
Anti Tumor Activity ◽  
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Introduction: The monolayer cell culture model is a popular model for screening anti-tumor activity of plant extracts. However, almost the extracts selected for screening in this model have failed in subsequent animal models. Therefore, there is only about 5 % of candidates from the original thousands of drugs that are screened which ultimately reach clinical trial. This study aimed to compare the differences in anti-tumor activity of 34 plant extracts against breast cancer cells in 2 models of monolayer cell culture (2D) and in three-dimensional (3D) cell culture. Methods: Four breast cancer cell lines (MCF-7, CD44+CD24- MCF-7, VN9, and CD44+CD24- VN9) were used to generate the 2D and 3D models (the 3D model was developed by culturing breast cancer cells in matrigel). The extracts were got from the plant extract library that prepared in the previous study. The anti-tumor activity was evaluated via half inhibitory concentrations( IC50 values). Results: Of the 34 extracts, E12, E7, E5 and E6 of them had an effect on MCF-7, CD44+CD24- MCF-7, VN9 and CD44+CD24- VN9 cells, respectively. The results indicated 10 potentially strong candidates for future drug development targeting hypoxic areas in breast cancer. Conclusion: The 3D culture model exhibited higher resistance to extracts than the 2D culture model. The CD44+CD24- cell population of both VN9 and MCF-7 cell lines showed higher drug resistance than the original cell lines (VN9 and MCF-7).  

scholarly journals Characterising the Response of Human Breast Cancer Cells to Polyamine Modulation

Biomolecules ◽  
2021 ◽  
Vol 11 (5) ◽  
pp. 743
Author(s):  
Oluwaseun Akinyele ◽  
Heather M. Wallace
Keyword(s):  
Breast Cancer ◽  
Cell Proliferation ◽  
Cell Growth ◽  
Cancer Cells ◽  
Cell Lines ◽  
Cancer Cell ◽  
Breast Cancer Cells ◽  
Growth Responses ◽  
Cancer Management ◽  
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Breast cancer is a complex heterogeneous disease with multiple underlying causes. The polyamines putrescine, spermidine, and spermine are polycationic molecules essential for cell proliferation. Their biosynthesis is upregulated in breast cancer and they contribute to disease progression. While elevated polyamines are linked to breast cancer cell proliferation, there is little evidence to suggest breast cancer cells of different hormone receptor status are equally dependent on polyamines. In this study, we characterized the responses of two breast cancer cells, ER+ (oestrogen receptor positive) MCF-7 and ER- MDA-MB-231 cell lines, to polyamine modulation and determined the requirement of each polyamine for cancer cell growth. The cells were exposed to DFMO (a polyamine pathway inhibitor) at various concentrations under different conditions, after which several growth parameters were determined. Exposure of both cell lines to DFMO induced differential growth responses, MCF-7 cells showed greater sensitivity to polyamine pathway inhibition at various DFMO concentrations than the MDA-MB-231 cells. Analysis of intracellular DFMO after withdrawal from growth medium showed residual DFMO in the cells with concomitant decreases in polyamine content, ODC protein level, and cell growth. Addition of exogenous polyamines reversed the cell growth inhibition, and this growth recovery appears to be partly dependent on the spermidine content of the cell. Similarly, DFMO exposure inhibits the global translation state of the cells, with spermidine addition reversing the inhibition of translation in the breast cancer cells. Taken together, these data suggest that breast cancer cells are differentially sensitive to the antitumour effects of polyamine depletion, thus, targeting polyamine metabolism might be therapeutically beneficial in breast cancer management based on their subtype.

scholarly journals Comparison of the effect of rhodium citrate-associated iron oxide nanoparticles on metastatic and non-metastatic breast cancer cells

2019 ◽  
Vol 10 (1) ◽  
Author(s):  
Natalia Lemos Chaves ◽  
Danilo Aquino Amorim ◽  
Cláudio Afonso Pinho Lopes ◽  
Irina Estrela-Lopis ◽  
Julia Böttner ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Cells ◽  
Cell Lines ◽  
Breast Cancer Cells ◽  
Human Tumor ◽  
Metastatic Breast ◽  
Cytotoxic Action ◽  
Dependent Manner ◽  
Metastatic Cells ◽  
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Abstract Background Nanocarriers have the potential to improve the therapeutic index of currently available drugs by increasing drug efficacy, lowering drug toxicity and achieving steady-state therapeutic levels of drugs over an extended period. The association of maghemite nanoparticles (NPs) with rhodium citrate (forming the complex hereafter referred to as MRC) has the potential to increase the specificity of the cytotoxic action of the latter compound, since this nanocomposite can be guided or transported to a target by the use of an external magnetic field. However, the behavior of these nanoparticles for an extended time of exposure to breast cancer cells has not yet been explored, and nor has MRC cytotoxicity comparison in different cell lines been performed until now. In this work, the effects of MRC NPs on these cells were analyzed for up to 72 h of exposure, and we focused on comparing NPs’ therapeutic effectiveness in different cell lines to elect the most responsive model, while elucidating the underlying action mechanism. Results MRC complexes exhibited broad cytotoxicity on human tumor cells, mainly in the first 24 h. However, while MRC induced cytotoxicity in MDA-MB-231 in a time-dependent manner, progressively decreasing the required dose for significant reduction in cell viability at 48 and 72 h, MCF-7 appears to recover its viability after 48 h of exposure. The recovery of MCF-7 is possibly explained by a resistance mechanism mediated by PGP (P-glycoprotein) proteins, which increase in these cells after MRC treatment. Remaining viable tumor metastatic cells had the migration capacity reduced after treatment with MRC (24 h). Moreover, MRC treatment induced S phase arrest of the cell cycle. Conclusion MRC act at the nucleus, inhibiting DNA synthesis and proliferation and inducing cell death. These effects were verified in both tumor lines, but MDA-MB-231 cells seem to be more responsive to the effects of NPs. In addition, NPs may also disrupt the metastatic activity of remaining cells, by reducing their migratory capacity. Our results suggest that MRC nanoparticles are a promising nanomaterial that can provide a convenient route for tumor targeting and treatment, mainly in metastatic cells.

scholarly journals Evaluation of the Impact of Imprinted Polymer Particles on Morphology and Motility of Breast Cancer Cells by Using Digital Holographic Cytometry

2020 ◽  
Vol 10 (3) ◽  
pp. 750 ◽  
Author(s):  
Megha Patel ◽  
Marek Feith ◽  
Birgit Janicke ◽  
Kersti Alm ◽  
Zahra El-Schich
Keyword(s):  
Breast Cancer ◽  
Sialic Acid ◽  
Cancer Cells ◽  
Cell Lines ◽  
Cell Morphology ◽  
Molecularly Imprinted Polymers ◽  
Breast Cancer Cells ◽  
Molecularly Imprinted ◽  
Imprinted Polymers ◽  
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Breast cancer is the second most common cancer type worldwide and breast cancer metastasis accounts for the majority of breast cancer-related deaths. Tumour cells produce increased levels of sialic acid (SA) that terminates the monosaccharide on glycan chains of the glycosylated proteins. SA can contribute to cellular recognition, cancer invasiveness and increase the metastatic potential of cancer cells. SA-templated molecularly imprinted polymers (MIPs) have been proposed as promising reporters for specific targeting of cancer cells when deployed in nanoparticle format. The sialic acid-molecularly imprinted polymers (SA-MIPs), which use SA for the generation of binding sites through which the nanoparticles can target and stain breast cancer cells, opens new strategies for efficient diagnostic tools. This study aims at monitoring the effects of SA-MIPs on morphology and motility of the epithelial type MCF-7 and the highly metastatic MDAMB231 breast cancer cell lines, using digital holographic cytometry (DHC). DHC is a label-free technique that is used in cell morphology studies of e.g., cell volume, area and thickness as well as in motility studies. Here, we show that MCF-7 cells move slower than MDAMB231 cells. We also show that SA-MIPs have an effect on cell morphology, motility and viability of both cell lines. In conclusion, by using DH microscopy, we could detect SA-MIPs impact on different breast cancer cells regarding morphology and motility.

scholarly journals NLRP3 as Putative Marker of Ipilimumab-Induced Cardiotoxicity in the Presence of Hyperglycemia in Estrogen-Responsive and Triple-Negative Breast Cancer Cells

2020 ◽  
Vol 21 (20) ◽  
pp. 7802 ◽  
Author(s):  
Vincenzo Quagliariello ◽  
Michelino De Laurentiis ◽  
Stefania Cocco ◽  
Giuseppina Rea ◽  
Annamaria Bonelli ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Cells ◽  
Cell Lines ◽  
Triple Negative Breast Cancer ◽  
High Glucose ◽  
Breast Cancer Cells ◽  
Triple Negative ◽  
Anticancer Efficacy ◽  
Low Glucose ◽  
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Hyperglycemia, obesity and metabolic syndrome are negative prognostic factors in breast cancer patients. Immune checkpoint inhibitors (ICIs) have revolutionized cancer treatment, achieving unprecedented efficacy in multiple malignancies. However, ICIs are associated with immune-related adverse events involving cardiotoxicity. We aimed to study if hyperglycemia could affect ipilimumab-induced anticancer efficacy and enhance its cardiotoxicity. Human cardiomyocytes and estrogen-responsive and triple-negative breast cancer cells (MCF-7 and MDA-MB-231 cell lines) were exposed to ipilimumab under high glucose (25 mM); low glucose (5.5 mM); high glucose and co-administration of SGLT-2 inhibitor (empagliflozin); shifting from high glucose to low glucose. Study of cell viability and the expression of new putative biomarkers of cardiotoxicity and resistance to ICIs (NLRP3, MyD88, cytokines) were quantified through ELISA (Cayman Chemical) methods. Hyperglycemia during treatment with ipilimumab increased cardiotoxicity and reduced mortality of breast cancer cells in a manner that is sensitive to NLRP3. Notably, treatment with ipilimumab and empagliflozin under high glucose or shifting from high glucose to low glucose reduced significantly the magnitude of the effects, increasing responsiveness to ipilimumab and reducing cardiotoxicity. To our knowledge, this is the first evidence that hyperglycemia exacerbates ipilimumab-induced cardiotoxicity and decreases its anticancer efficacy in MCF-7 and MDA-MB-231 cells. This study sets the stage for further tests on other breast cancer cell lines and primary cardiomyocytes and for preclinical trials in mice aimed to decrease glucose through nutritional interventions or administration of gliflozines during treatment with ipilimumab.

Synergistic inhibition of breast cancer cell lines with the combination of a dual inhibitor of EGFR/HER-2/neu and a Bcl-2 inhibitor

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 13100-13100
Author(s):  
L. Witters ◽  
A. Witkoski ◽  
M. Planas-Silva ◽  
J. Viallet ◽  
M. S. Berger ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Cells ◽  
Cell Lines ◽  
Human Breast Cancer ◽  
Breast Cancer Cells ◽  
Human Breast Cancer Cells ◽  
Human Breast ◽  
Dual Inhibitor ◽  
Her 2 ◽  
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13100 Background: The epidermal growth factor receptor (EGFR; ErbB1) and HER-2/neu (ErbB2), members of the ErbB family of receptor tyrosine kinases, are overexpressed in a variety of human tumors and overexpression generally correlates with poor prognosis and decreased survival. Use of inhibitors of these receptors as monotherapies, e.g., trastuzumab, Iressa, and erlotinib, has led to advances in treatment, but many patients do not respond or develop resistance. The anti-apoptotic protein, Bcl-2, is also overexpressed in a number of human tumors. Inhibitors of Bcl-2 induce apoptosis and sensitize cancer cells to other therapies. This study assesses the effects of a combination of a reversible inhibitor of both EGFR and HER-2/neu that is similar to lapatinib (GW2974) and a pan inhibitor of the Bcl-2 family (GX15–070: Gemin X Biotechnologies, Inc.) on the growth of human breast cancer cells. Methods: The MCF-7 human breast cancer cell line transfected with a control vector, MCF/neo, and the HER-2/neu transfected MCF-7 cell line, MCF/18, were treated with various concentrations of GW2974 (0.25–10 μM) and/or the GX15–070 pan Bcl-2 inhibitor (50–500 nM). After a 3 day exposure, cell number was determined using the colorimetric MTT tetrazolium dye assay. Percent of control was normalized to corresponding concentrations of the solvent for both agents (DMSO). Results: Treatment with the GW2974 dual inhibitor or the GX15–070 pan Bcl-2 inhibitor resulted in dose-dependent growth inhibition in both the control and HER-2/neu transfected MCF-7 cell lines. The combination of both agents produced synergistic growth inhibition in both cell lines as confirmed by isobologram analysis. Conclusions: This study has demonstrated synergy with the combination of a dual inhibitor of EGFR and HER-2/neu and an inhibitor of Bcl-2 in control and HER-2/neu overexpressing MCF-7 human breast cancer cells. This finding warrants an evaluation of this combination in clinical trials for the treatment of patients with metastatic breast cancer. [Table: see text]

scholarly journals Proton pump inhibitors enhance chemosensitivity, promote apoptosis, and suppress migration of breast cancer cells

2020 ◽  
Vol 70 (2) ◽  
pp. 179-190 ◽  
Author(s):  
Worood G. Ihraiz ◽  
Mamoun Ahram ◽  
Sanaa K. Bardaweel
Keyword(s):  
Breast Cancer ◽  
Cell Migration ◽  
Synergistic Effect ◽  
Cancer Cells ◽  
Cell Lines ◽  
Proton Pump ◽  
Breast Cancer Cells ◽  
Combined Treatment ◽  
Combined Effects ◽  
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AbstractBreast cancer is the most common cancer and is the leading cause of cancer deaths among women worldwide. Despite the availability of numerous therapeutics for breast cancer management, cytotoxicity and emergence of drug resistance are major challenges that limit their benefits. The acidic microenvironment surrounding tumor cells is a common feature inducing cancer cell invasiveness and chemoresistance. Proton pump inhibitors (PPIs) are one of the most commonly prescribed drugs for the treatment of acid-related conditions. PPIs have been reported to exhibit antitumorigenic effects in many cancer types. In this study, the anti-proliferative and anti-migratory effects of PPIs in three breast cancer cell lines; MCF-7, T47D, and MDA-MB-231 cells, have been investigated. In addition, the combined effects of PPIs with anticancer drugs, as well as the mechanism of PPI-mediated anti-proliferative activity were evaluated. The anti-proliferative and combined effects of PPIs were evaluated by MTT assay. Cell migration was assessed using the wound-healing assay. The mechanism of cell death was assessed using annexin V-FITC/propidium iodide staining flow cytometry method. Our results indicated that PPIs treatment significantly inhibited the growth of breast cancer cells in a dose-dependent manner. The antiproliferative activity of PPIs was significantly induced by apoptosis in all tested cell lines. The combined treatment of PPIs with doxorubicin resulted in a synergistic effect in all cell lines, whereas the combined treatment with raloxifene exhibited synergistic effect in T47D cells only and additive effects in MDA-MB-231 and MCF-7 cells. In addition, PPIs treatment significantly reduced cell migration in MDA-MB-231 cells. In conclusion, the addition of PPIs to the treatment regimen of breast cancer appears to be a promising strategy to potentiate the efficacy of chemotherapy and may suppress cancer metastasis.

scholarly journals lncMat2B regulated by severe hypoxia induces cisplatin resistance by increasing DNA damage repair and tumor-initiating population in breast cancer cells

2020 ◽  
Vol 41 (11) ◽  
pp. 1485-1497 ◽  
Author(s):  
Alfredo García-Venzor ◽  
Edna Ayerim Mandujano-Tinoco ◽  
Araceli Ruiz-Silvestre ◽  
José Manuel Sánchez ◽  
Floria Lizarraga ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Dna Damage ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Ectopic Expression ◽  
Three Dimensional ◽  
Severe Hypoxia ◽  
Loss Of Function ◽  
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Abstract Multicellular tumor spheroids (MCTSs) constitute a three-dimensional culture system that recapitulates the in vivo tumor microenvironment. Tumor cells cultured as MCTSs present antineoplastic resistance due to the effect of microenvironmental signals acting upon them. In this work, we evaluated the biological function of a new microenvironment-regulated long non-coding RNA, lncMat2B, in breast cancer. In MCTSs, the expression of lncMat2B presented an increase and a zonal heterogeneity, as it was expressed principally in quiescent cells of hypoxic regions of the MCTSs. As expected, functional assays supported the role of severe hypoxia in the regulation of lncMat2B. Moreover, gain- and loss-of-function assays using a transcriptional silencing CRISPR/Cas9 system and gBlock revealed that lncMAT2B regulates the tumor-initiating phenotype. Interestingly, lncMat2B is overexpressed in a cisplatin-resistant MCF-7 cell line, and its ectopic expression in wild type MCF-7 cells increased survival to cisplatin exposure by reducing DNA damage and reactive oxygen species accumulation. lncMAT2B is a possible link between severe hypoxia, tumor-initiating phenotype and drug resistance in breast cancer cells.

Synthesis and In Vitro Evaluation of Tetrahydroquinoline Derivatives as Antiproliferative Compounds of Breast Cancer via Targeting the GPER

2019 ◽  
Vol 19 (6) ◽  
pp. 760-771 ◽  
Author(s):  
Oscar J. Zacarías-Lara ◽  
David Méndez-Luna ◽  
Gustavo Martínez-Ruíz ◽  
José R. García-Sanchéz ◽  
Manuel J. Fragoso-Vázquez ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cell Proliferation ◽  
Cancer Cells ◽  
Cell Lines ◽  
In Silico ◽  
Breast Cancer Cells ◽  
Breast Cancer Cell Lines ◽  
In Silico Studies ◽  
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Background: Some reports have demonstrated the role of the G Protein-coupled Estrogen Receptor (GPER) in growth and proliferation of breast cancer cells. Objective: In an effort to develop new therapeutic strategies against breast cancer, we employed an in silico study to explore the binding modes of tetrahydroquinoline 2 and 4 to be compared with the reported ligands G1 and G1PABA. Methods: This study aimed to design and filter ligands by in silico studies determining their Lipinski's rule, toxicity and binding properties with GPER to achieve experimental assays as anti-proliferative compounds of breast cancer cell lines. Results: In silico studies suggest as promissory two tetrahydroquinoline 2 and 4 which contain a carboxyl group instead of the acetyl group (as is needed for G1 synthesis), which add low (2) and high hindrance (4) chemical moieties to explore the polar, hydrophobic and hindrance effects. Docking and molecular dynamics simulations of the target compounds were performed with GPER to explore their binding mode and free energy values. In addition, the target small molecules were synthesized and assayed in vitro using breast cancer cells (MCF-7 and MDA-MB-231). Experimental assays showed that compound 2 decreased cell proliferation, showing IC50 values of 50µM and 25µM after 72h of treatment of MCF-7 and MDA-MB-231 cell lines, respectively. Importantly, compound 2 showed a similar inhibitory effect on proliferation as G1 compound in MDA-MB-231 cells, suggesting that both ligands reach the GPER-binding site in a similar way, as was demonstrated through in silico studies. Conclusion: A concentration-dependent inhibition of cell proliferation occurred with compound 2 in the two cell lines regardless of GPER.

The synergistic effect between celecoxib and luteolin and dependence on estrogen receptor in human breast cancer cells.

2015 ◽  
Vol 33 (28_suppl) ◽  
pp. 135-135
Author(s):  
Ye-Won Jeon ◽  
Youngjin Suh
Keyword(s):  
Breast Cancer ◽  
Cancer Cells ◽  
Cell Lines ◽  
Combination Treatment ◽  
Breast Cancer Cells ◽  
Synergistic Effects ◽  
Breast Cancer Cell Lines ◽  
Human Breast ◽  
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135 Background: The anti-cancer effects of celecoxib and luteolin are well known. Although our previous study demonstrated that the combination of celecoxib and luteolin synergistically inhibits breast tumor growth compared with each of the treatments alone, we did not uncover the molecular mechanisms of these effects. The aims of our present study were to compare the effects of a celecoxib and luteolin combination treatment in four different human breast cell lines and to determine the mechanisms of action in vitro and in vivo. Methods: Using MCF-7, MCF7/HER18, MDA-MB-231 and SkBr3 human breast cancer cells, proliferation assay, apoptosis assay, inhibition assay with MEK and PI3K inhibitor in addition to western blotting and xenograft study after treatment with celecoxib and luteolin. Results: The synergistic effects of a celecoxib and luteolin combination treatment yielded significantly greater cell growth inhibition in all four breast cancer cell lines compared with the single agents alone. In particular, combined celecoxib and luteolin treatment significantly decreased the growth of MDA-MB-231 cancer cells in vivo compared with either agent alone. The celecoxib and luteolin combination treatment induced synergistic effects via Akt inactivation and extracellular signal-regulated kinase (ERK) signaling inhibition in MCF-7 and MCF7/HER18 cells and via Akt inactivation and ERK signaling activation in MDA-MB-231 and SkBr3 cells. Conclusions: These results demonstrate the synergistic anti-tumor effect of the celecoxib and luteolin combination treatment in different four breast cancer cell lines, thus introducing the possibility of this combination as a new treatment modality.

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