scholarly journals Malic enzyme 1 may be a novel target of breast cancer metastasis

2019 ◽  
Author(s):  
Chang Liu ◽  
Shuchen Lin ◽  
Yannan Zhao ◽  
Jun Cao ◽  
Zhonghua Tao ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cell Lines ◽  
Malic Enzyme ◽  
Prognostic Value ◽  
Cancer Metastasis ◽  
Breast Cancer Metastasis ◽  
Breast Cancer Cell Lines ◽  
Public Database ◽  
The Public ◽  
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Abstract Background Malic enzyme 1 (ME1) catalyzes malate to pyruvate and thus promotes glycolysis, playing a part in the Warburg effect. It also has a potential role in tumor progression, but its function in breast cancer remains to be fully clarified. This work aimed to investigate the prognostic value of ME1 and its possible mechanism in breast cancer.Methods We evaluated ME1 expression in 220 early breast cancer patients with tissue microarray-based immunohistochemistry and explored the relationships between ME1 expression and clinicopathological features. Survival analyses were further performed to determine its prognostic value. The public database was used to confirm tissue microarray results. Moreover, we profiled ME1 expression in breast cancer cell lines via western blotting, and then assessed it in cell viability and motility via Cell counting kit-8 (CCK-8), colony formation, transwell migration and invasion assays. Reactive oxygen species (ROS) was detected by dihydroethidium (DHE) and 2’,7’-Dichlorodihydrofluorescein diacetate (DCFH-DA).Results In breast cancer tissues, high ME1 expression was significantly associated with larger tumor size, more lymph node metastasis and more extensive lymph-vascular invasion. Survival analysis showed high ME1 expression was significantly correlated with worse recurrence free survival (RFS). Multivariate analysis further identified high ME1 expression as an independent prognostic factor for RFS, which was confirmed by mRNA results in the public database. In vitro , human epidermal growth factor receptor-2 positive and triple negative breast cancer cell lines showed higher expression of ME1, while Luminal cell lines showed lower expression of ME1. Upregulation of ME1 by transfecting MCF-7 cells with virus vector remarkably enhanced viability and motility, epithelial-mesenchymal transition (EMT), and decreased ROS levels, whereas knockdown of this gene in MDA-MB-468 cells produced totally opposite effects as expected. More important, when pretreated with hydrogen peroxide, an oxidizing agent, MCF-7 cells overexpressing ME1 lost its motility, whereas MDA-MB-468 cells with knock-down of ME1 restored its motility when pretreated with N-acetyl cysteine, an antioxidant.Conclusions To our knowledge, these clinical and experiment work first suggested that ME1 may be a potential therapeutic target for breast cancer metastasis, and its biological effect is mainly controlled by manipulating ROS.

scholarly journals Integrated Transcriptomics, Proteomics, and Glycomics Reveals the Association between Up-regulation of Sialylated N-glycans/Integrin and Breast Cancer Brain Metastasis

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Wenjing Peng ◽  
Rui zhu ◽  
Shiyue Zhou ◽  
Parvin Mirzaei ◽  
Yehia Mechref
Keyword(s):  
Breast Cancer ◽  
Brain Metastasis ◽  
Cell Line ◽  
Cell Lines ◽  
Cancer Cell ◽  
Cancer Metastasis ◽  
Cancer Cell Line ◽  
Breast Cancer Metastasis ◽  
Breast Cancer Cell Lines ◽  
Breast Cancer Brain Metastasis

AbstractBreast cancer brain metastasis has been recognized as one of the central issues in breast cancer research. The elucidation of the processes and pathways that mediate this step will provide important clues for a better understanding of breast cancer metastasis. Increasing evidence suggests that aberrant glycosylation patterns greatly contribute to cell invasion and cancer metastasis. Herein, we combined next-generation RNA sequencing with liquid chromatography-tandem mass spectrometry-based proteomic and N-glycomic analysis from five breast cancer cell lines and one brain cancer cell line to investigate the possible mechanisms of breast cancer brain metastasis. The genes/proteins associated with cell movement were highlighted in breast cancer brain metastasis. The integrin signaling pathway and the up-regulation of α-integrin (ITGA2, ITGA3) were associated with the brain metastatic process. 12 glycogenes showed unique expression in 231BR, which could result in an increase of sialylation during brain metastasis. In agreement with the changes of glycogenes, 60 out of 63 N-glycans that were identified exhibited differential expression among cell lines. The correlation between glycogenes and glycans revealed the importance of sialylation and sialylated glycans in breast cancer brain metastasis. Highly sialylated N-glycans, which were up-regulated in brain-seeking cell line 231BR, likely play a role in brain metastasis.

Cytotoxic activity and anti-cancer potential of Ontario grown onion extracts against breast cancer cell lines

2018 ◽  
Vol 8 (3) ◽  
pp. 159 ◽  
Author(s):  
Meghan Fragis ◽  
Abdulmonem I. Murayyan ◽  
Suresh Neethirajan
Keyword(s):  
Breast Cancer ◽  
Cytotoxic Activity ◽  
Cell Lines ◽  
Cancer Cell ◽  
Breast Cancer Cell ◽  
Cancer Cell Lines ◽  
Breast Cancer Cell Lines ◽  
Cytotoxic Activities ◽  
Cancer Line ◽  
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Background: Breast cancer is the most commonly diagnosed cancer and the second leading cause of cancer deaths among Canadian women. Cancer management through changes in lifestyle, such as increased intake of foods rich in dietary flavonoids, have been shown to decrease the risk associated with breast, liver, colorectal, and upper-digestive cancers in epidemiologic studies. Onions are high in flavonoid content and one of the most common vegetables. Additionally, onions are used in most Canadian cuisines.Methods: We investigated the effect of five prominent Ontario grown onion (Stanley, Ruby Ring, LaSalle, Fortress, and Safrane) extracts on two subtypes of breast cancer cell lines: a triple negative breast cancer line MDA-MB-231 and an ER+ breast cancer line MCF-7.Results: These onion extracts elicited strong anti-proliferative, anti-migratory, and cytotoxic activities on both the cancer cell lines. Flavonoids present in these onion extracts induced apoptosis, cell cycle arrest in the G2/M phase, and a reduction in mitochondrial membrane potential at dose-dependent concentrations. Onion extracts were more effective against MDA-MB-231 compared to the MCF-7 cell line. Conclusion: In this study, we investigated the extracts synthesized from Ontario-grown onion varieties in inducing anti-migratory, cytostatic, and cytotoxic activities in two sub-types of human breast cancer cell lines. Anti-tumor activity of these extracts depends upon the varietal and can be formulated into nutraceuticals and functional foods for the wellbeing of cancer patients. Overall, the results suggest that onion extracts are a good source of flavonoids with anti-cancerous properties.Keywords: onion extracts; flavonoids; anti-proliferative; breast cancer; cytotoxic activity

Thieno[2,3-d]pyrimidin-4(3H)-one Derivatives of Benzimidazole as Potential Anti-Breast Cancer (MDA-MB-231, MCF-7) Agents.

2020 ◽  
Vol 20 ◽  
Author(s):  
Stefan Dimov ◽  
Anelia Ts. Mavrova ◽  
Denitsa Yancheva ◽  
Biliana Nikolova ◽  
Iana Tsoneva
Keyword(s):  
Breast Cancer ◽  
Cell Lines ◽  
Mechanism Of Action ◽  
Biologically Active ◽  
Breast Cancer Cell Lines ◽  
3T3 Cells ◽  
Fluorescence Study ◽  
Compound 21 ◽  
Mutational Activation ◽  
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Aims: The purpose was the synthesis of some new thienopyrimidines derivative of 1,3-disubstituted benzimidazoles and the evaluation of their cytotoxicity towards MDA-MB-231 and MCF-7 cell lines as well 3T3 cells. Background: An overexpression or mutational activation of TK receptors EGFR and HER2/neu are characteristic for tumors. It has been found that some thieno[2,3-d]pyrimidines exhibit better inhibitory activity against epidermal growth factor receptor (EGFR/ErbB-2) tyrosine kinase in comparison to aminoquinazolines. Breast cancer activity towards MDAMB-231 and MCF-7 cell lines by inhibiting EGFR was revealed by a novel 2-arylbenzimidazole. This motivated the synthesis of new thienopyrimidines possessing benzimidazole fragment in order to evaluate their cytotoxicity to the above mentioned cell lines. Objective: The objectives were the design and synthesis of a novel series thieno[2,3-d]pyrimidines bearing biologically active moieties as 1,3-disubstituted-benzimidazole heterocycle structurally similar to diaryl ureas in order to evaluate their cytotoxicity against MDA-MB-231, MCF-7 breast cancer cell lines. Methods: N,N-disubstituted benzimidazole-2-one carbonitriles were synthesized by Aza-Michael addition and used as precursors to generate some of the new thieno[2,3-d]pyrimidines in acidic medium. The interaction of chloroethyl-2- thienopyrimidines and 2-amino-benzimidazole resp. benzimidazol-2-one nitriles under solid-liquid transfer catalysis conditions lead to obtaining of new thienopyrimidines. MTT assay for cells survival was performed in order to establish the cytotoxicity of the tested compounds. Fluorescence study was used to elucidate some aspect of mechanism. Results: The effect of nine of the synthesized compounds was investigated towards MDA-MB-231 and MCF-7 cells as well as to 3T3 cells. Thieno[2,3-d]pyirimidine-4-one 16 (IC50 – 0.058 μM) and 21 (IC50 – 0.029 μM) possess high cytotoxicity against MDA-MB-231 cells after 24h. The most toxic against breast cancer MCF-7 cells was compounds 21 (IC50 – 0.074 μM), revealing lower cytotoxicity towards mouse fibroblast 3T3 cells with IC50 – 0.20 μM. SAR analisys was performed. Fluorescence study of the treatment of MDA-MB cells with compound 21 was carried out in order to clarify some aspects of mechanism of action. Conclusion: The relationship between cytotoxicity of compounds 14 and 20 against MCF-7 and 3T3 cells can suggest a similar mechanism of action. The antitumor potential of the tested compounds proves the necessity for further investigation to estimate the exact inhibition pathway in the cellular processes. The fluorescence study of the treatment of MDA-MB cells with compound 21 showed a rapid process of apoptosis.

scholarly journals Factors modulating integrin Beta I expression on the breast cancer cell lines MCF-7 and MDA-MB-231

2000 ◽  
Vol 2 (S1) ◽  
Author(s):  
CJ Pogson ◽  
CMW Chan ◽  
L-A Martin ◽  
GPH Gui ◽  
M Dowsett
Keyword(s):  
Breast Cancer ◽  
Cell Lines ◽  
Cancer Cell ◽  
Breast Cancer Cell ◽  
Cancer Cell Lines ◽  
Breast Cancer Cell Lines ◽  
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scholarly journals In vitro investigation of cytotoxic and antioxidative activities of Ardisia crispa against breast cancer cell lines, MCF-7 and MDA-MB-231

2018 ◽  
Vol 18 (1) ◽  
Author(s):  
Muhammad Luqman Nordin ◽  
Arifah Abdul Kadir ◽  
Zainul Amiruddin Zakaria ◽  
Rasedee Abdullah ◽  
Muhammad Nazrul Hakim Abdullah
Keyword(s):  
Breast Cancer ◽  
Cell Lines ◽  
Cancer Cell ◽  
Breast Cancer Cell ◽  
Cancer Cell Lines ◽  
Breast Cancer Cell Lines ◽  
In Vitro Investigation ◽  
Ardisia Crispa ◽  
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scholarly journals A Bottom-Up Synthesis Approach to Silver Nanoparticles Induces Anti-Proliferative and Apoptotic Activities Against MCF-7, MCF-7/TAMR-1 and MCF-10A Human Breast Cell Lines

Molecules ◽  
2020 ◽  
Vol 25 (18) ◽  
pp. 4332
Author(s):  
Nurul Izzati Zulkifli ◽  
Musthahimah Muhamad ◽  
Nur Nadhirah Mohamad Zain ◽  
Wen-Nee Tan ◽  
Noorfatimah Yahaya ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Silver Nanoparticles ◽  
Cell Lines ◽  
Leaf Extract ◽  
Breast Cancer Cell Lines ◽  
Face Centered Cubic ◽  
Human Breast ◽  
Bottom Up ◽  
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A bottom-up approach for synthesizing silver nanoparticles (AgNPs-GA) phytomediated by Garcinia atroviridis leaf extract is described. Under optimized conditions, the AgNPs-GA were synthesized at a concentration of 0.1 M silver salt and 10% (w/v) leaf extract, 1:4 mixing ratio of reactants, pH 3, temperature 32 °C and 72 h reaction time. The AgNPs-GA were characterized by various analytical techniques and their size was determined to be 5–30 nm. FTIR spectroscopy indicates the role of phenolic functional groups in the reduction of silver ions into AgNPs-GA and in supporting their subsequent stability. The UV-Visible spectrum showed an absorption peak at 450 nm which reflects the surface plasmon resonance (SPR) of AgNPs-GA and further supports the stability of these biosynthesized nanoparticles. SEM, TEM and XRD diffractogram analyses indicate that AgNPs-GA were spherical and face-centered-cubic in shape. This study also describes the efficacy of biosynthesized AgNPs-GA as anti-proliferative agent against human breast cancer cell lines, MCF-7 and MCF-7/TAMR-1. Our findings indicate that AgNPs-GA possess significant anti-proliferative effects against both the MCF-7 and MCF-7/TAMR-1 cell lines, with inhibitory concentration at 50% (IC50 values) of 2.0 and 34.0 µg/mL, respectively, after 72 h of treatment. An induction of apoptosis was evidenced by flow cytometry using Annexin V-FITC and propidium iodide staining. Therefore, AgNPs-GA exhibited its anti-proliferative activity via apoptosis on MCF-7 and MCF-7/TAMR-1 breast cancer cells in vitro. Taken together, the leaf extract from Garcinia atroviridis was found to be highly capable of producing AgNPs-GA with favourable physicochemical and biological properties.

scholarly journals Integrative analysis of mRNA and miRNA profiles identifies miR-193 and miR-210 as potential regulatory biomarkers in different molecular subtypes of breast cancer

2020 ◽  
Author(s):  
Adriane Feijo Evangelista ◽  
Renato J Oliveira ◽  
Viviane A O Silva ◽  
Rene A D C Vieira ◽  
Rui M Reis ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cell Proliferation ◽  
Cell Line ◽  
Cell Lines ◽  
Breast Cancer Cell ◽  
Cancer Progression ◽  
Triple Negative ◽  
Molecular Subtypes ◽  
Breast Cancer Cell Lines ◽  
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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.

scholarly journals The role of miRNAs 34a, 146a, 320a and 542 in the synergistic anticancer effects of methyl 2-(5-fluoro-2-hydroxyphenyl)-1H- benzo[d]imidazole-5-carboxylate (MBIC) with doxorubicin in breast cancer cells

PeerJ ◽  
2018 ◽  
Vol 6 ◽  
pp. e5577 ◽  
Author(s):  
Mohadeseh Hasanpourghadi ◽  
Nazia Abdul Majid ◽  
Mohd Rais Mustafa
Keyword(s):  
Breast Cancer ◽  
Cell Lines ◽  
Cancer Cell ◽  
Breast Cancer Cell ◽  
Breast Cancer Cells ◽  
Cancer Cell Lines ◽  
Human Breast Cancer Cell ◽  
Breast Cancer Cell Lines ◽  
Human Breast ◽  
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Combination Index (CI) analysis suggested that MBIC and doxorubicin synergistically inhibited up to 97% of cell proliferation in ER+/PR+MCF-7 and triple negative MDA-MB-231 breast cancer cell lines. Moreover, treatment of the breast cancer cells with the combined drugs resulted in lower IC50 values in contrast to the individual drug treatment. Small noncoding microRNAs (miRNA) may function as non-mutational gene regulators at post-transcriptional level of protein synthesis. In the present study, the effect of the combined treatment of MBIC and doxorubicin on the expression level of several miRNAs including miR-34a, miR-146a, miR-320a and miR-542 were evaluated in MCF-7 and MDA-MB-231 breast cancer cell lines. These miRNAs have the potential to alter the protein level of survivin, the anti-apoptotic protein and reduce the metastatic activity in human breast cancer cell lines by interfering with the nuclear accumulation of NF-κB. Our results demonstrated the several fold changes in expression of miRNAs, which is drug and cell line dependent. This finding demonstrated a functional synergistic network between miR-34a, miR-320a and miR-542 that are negatively involved in post-transcriptional regulation of survivin in MCF-7 cells. While in MDA-MB-231 cells, changes in expression level of miR-146a was correlated with inhibition of the nuclear translocation of NF-κB. The overall result suggested that alteration in protein level and location of survivin and NF-κB by miR-34a, miR-320a, miR-146a and miR-542, remarkably influenced the synergistic enhancement of combined MBIC and doxorubicin in treatment of aggressive and less aggressive human breast cancer cell lines.

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