scholarly journals Spliceosome-Associated microRNAs Signify Breast Cancer Cells and Portray Potential Novel Nuclear Targets

2020 ◽  
Vol 21 (21) ◽  
pp. 8132
Author(s):  
Shelly Mahlab-Aviv ◽  
Keren Zohar ◽  
Yael Cohen ◽  
Ayelet R. Peretz ◽  
Tsiona Eliyahu ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cell Line ◽  
Cell Lines ◽  
Suppressor Gene ◽  
Breast Cancer Patients ◽  
Human Breast ◽  
Cancerous Cell ◽  
Nuclear Targets ◽  
Tumorigenic Cell Line ◽  
Mcf 7

MicroRNAs (miRNAs) act as negative regulators of gene expression in the cytoplasm. Previous studies have identified the presence of miRNAs in the nucleus. Here we study human breast cancer-derived cell-lines (MCF-7 and MDA-MB-231) and a non-tumorigenic cell-line (MCF-10A) and compare their miRNA sequences at the spliceosome fraction (SF). We report that the levels of miRNAs found in the spliceosome, their identity, and pre-miRNA segmental composition are cell-line specific. One such miRNA is miR-7704 whose genomic position overlaps HAGLR, a cancer-related lncRNA. We detected an inverse expression of miR-7704 and HAGLR in the tested cell lines. Specifically, inhibition of miR-7704 caused an increase in HAGLR expression. Furthermore, elevated levels of miR-7704 slightly altered the cell-cycle in MDA-MB-231. Altogether, we show that SF-miR-7704 acts as a tumor-suppressor gene with HAGLR being its nuclear target. The relative levels of miRNAs found in the spliceosome fractions (e.g., miR-100, miR-30a, and let-7 family) in non-tumorigenic relative to cancer-derived cell-lines was monitored. We found that the expression trend of the abundant miRNAs in SF was different from that reported in the literature and from the observation of large cohorts of breast cancer patients, suggesting that many SF-miRNAs act on targets that are different from the cytoplasmic ones. Altogether, we report on the potential of SF-miRNAs as an unexplored route for cancerous cell state.

scholarly journals Antiestrogen-resistant human breast cancer cells require activated Protein Kinase B/Akt for growth

2005 ◽  
Vol 12 (3) ◽  
pp. 599-614 ◽  
Author(s):  
T Frogne ◽  
J S Jepsen ◽  
S S Larsen ◽  
C K Fog ◽  
B L Brockdorff ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Patients ◽  
Cell Lines ◽  
Human Breast Cancer ◽  
Neutralizing Antibodies ◽  
Breast Cancer Cells ◽  
Resistant Cell ◽  
Breast Cancer Patients ◽  
Human Breast ◽  
Mcf 7

Development of acquired resistance to antiestrogens is a major clinical problem in endocrine treatment of breast cancer patients. The IGF system plays a profound role in many cancer types, including breast cancer. Thus, overexpression and/or constitutive activation of the IGF-I receptor (IGF-IR) or different components of the IGF-IR signaling pathway have been reported to render breast cancer cells less estrogen dependent and capable of sustaining cell proliferation in the presence of antiestrogens. In this study, growth of the antiestrogen-sensitive human breast cancer cell line MCF-7 was inhibited by treatment with IGF-IR-neutralizing antibodies. In contrast, IGF-IR-neutralizing antibodies had no effect on growth of two different antiestrogen-resistant MCF-7 sublines. A panel of antiestrogen-resistant cell lines was investigated for expression of IGF-IR and either undetectable or severely reduced IGF-IR levels were observed. No increase in insulin receptor substrate 1 (IRS-1) or total PKB/Akt (Akt) was detected in the resistant cell lines. However, a significant increase in phosphorylated Akt (pAkt) was found in four of six antiestrogen-resistant cell lines. Overexpression of pAkt was associated with increased Akt kinase activity in both a tamoxifen- and an ICI 182,780-resistant cell line. Inhibition of Akt phosphorylation by the phosphatidylinositol 3-kinase (PI3-K) inhibitor wortmannin or the Akt inhibitor SH-6 (structurally modified phosphatidyl inositol ether liquid analog PIA 6) resulted in a more pronounced growth inhibitory effect on the antiestrogen-resistant cells compared with the parental cells, suggesting that signaling via Akt is required for antiestrogen-resistant cell growth in at least a subset of our antiestrogen-resistant cell lines. PTEN expression and activity was not decreased in cell lines overexpressing pAkt. Our data demonstrate that Akt is a target for treatment of antiestrogen-resistant breast cancer cell lines and we suggest that antiestrogen-resistant breast cancer patients may benefit from treatment targeted to inhibit Akt signaling.

scholarly journals Chenopodium AlbumPrevents Progression of Cell Growth and Enhances Cell Toxicity in Human Breast Cancer Cell Lines

2009 ◽  
Vol 2 (3) ◽  
pp. 160-165 ◽  
Author(s):  
Menka Khoobchandani ◽  
B. K. Ojeswi ◽  
Bhavna Sharma ◽  
Man Mohan Srivastava
Keyword(s):  
Breast Cancer ◽  
Cell Line ◽  
Cell Lines ◽  
Cancer Cell ◽  
Breast Cancer Cell ◽  
Human Breast Cancer ◽  
Human Breast Cancer Cell ◽  
Breast Cancer Cell Lines ◽  
Human Breast ◽  
Mcf 7

The present study is aimed to investigate the effects ofChenopodium album(leaves) on the growth of estrogen dependent (MCF-7) and estrogen independent (MDA-MB-468) human breast cancer cell lines. The different solvent extracts (petroleum ether, ethyl acetate and methanol) were assessed for their cytotoxicity using TBE (Trypan blue exclusion) and MTT [3-(4, 5-dimethyl thiazol-2-yl)-2, 5-diphenyl tetrazolium] bioassay. These cells were cultured in MEM (minimum essential medium) medium and incubated with the dilution series of extracts (10–100 mg/ml) in CO2incubator at 37°C for 24 h. Among the various extracts studied for two cell lines, methanolic extract ofC. album(leaves) exhibited maximum antibreast cancer activity having IC50(the concentration of an individual compound leading to 50% inhibition) value 27.31 mg/ml against MCF-7 cell line. Significant percent inhibition (94.06%) in the MeOH extract ofC. album(leaves) at 48 h of exposure and concentration 100 mg/ml (p < 0.05) against MCF-7 breast cancer cell line, indicates the presence of some structural moiety responsible for this observed antiproliferative effect. In vivo study and structural elucidation of its bioactive principle are in progress. Our findings highlight the potential of this plant for its possible clinical use to counteract malignancy development as antibreast cancer bioagent.

scholarly journals Spliceosome-Associated MicroRNAs Identified in Breast Cancer Cells Act on Nuclear Targets and Are Potential Indicators for Tumorigenicity

2020 ◽  
Author(s):  
Shelly Mahlab-Aviv ◽  
Keren Zohar ◽  
Yael Cohen ◽  
Ayelet R. Peretz ◽  
Tsiona Eliyahu ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cell Lines ◽  
Breast Cancer Cells ◽  
Cancer Therapeutics ◽  
Breast Cancer Patients ◽  
Division Rate ◽  
Cell Division Rate ◽  
Mirnas Expression ◽  
Nuclear Targets ◽  
Mcf 7

AbstractMicroRNAs (miRNAs) act as negative regulators of gene expression in the cytoplasm. Previous studies identified miRNAs associated with the spliceosome. Here we study three breast-derived cell-lines with increased tumorigenicity (from MCF-10A to MCF-7 and MDA-MB-231) and compared their miRNA sequences at the spliceosome fraction (SF). We report that the SF-miRNAs expression, identity, and pre-miRNA segmental composition vary across these cell-lines. The expression of the majority of the abundant SF-miRNAs (e.g. miR-100, miR-30a, and let-7 members) shows an opposite trend in view of the literature and breast cancer large cohorts. The results suggest that SF-miRNAs act in the nucleus on alternative targets than in the cytoplasm. One such miRNA is miR-7704 whose genomic position overlaps HAGLR, a cancer-related lncRNA. We found an inverse expression of miR-7704 and HAGLR in the tested cell lines. Moreover, inhibition of miR-7704 caused an increase in HAGLR expression. Furthermore, increasing miR-7704 levels attenuated the MDA-MB-231 cell-division rate. While miR-7704 acts as oncomiR in breast cancer patients, it has a tumor-suppressing function in SF, with HAGLR being its nuclear target. Manipulating miR-7704 levels is a potential lead for altering tumorigenicity. Altogether, we report on the potential of manipulating SF-miRNAs as an unexplored route for breast cancer therapeutics.

scholarly journals MCF-7 Drug Resistant Cell Lines Switch Their Lipid Metabolism to Triple Negative Breast Cancer Signature

Cancers ◽  
2021 ◽  
Vol 13 (23) ◽  
pp. 5871
Author(s):  
Jose Adriá-Cebrián ◽  
Sandra Guaita-Esteruelas ◽  
Eric W.-F. Lam ◽  
Marta Rodríguez-Balada ◽  
Jordi Capellades ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Adipose Tissue ◽  
Palmitic Acid ◽  
Cell Line ◽  
Cell Lines ◽  
Cancer Prognosis ◽  
Breast Cancer Cell Lines ◽  
Breast Cancer Patients ◽  
Metabolic Pattern ◽  
Mcf 7

Obesity and adipose tissue have been closely related to a poor cancer prognosis, especially in prostate and breast cancer patients. The ability of transferring lipids from the adipose tissue to the tumor cells is actively linked to tumor progression. However, different types of breast tumor seem to use these lipids in different ways and metabolize them in different pathways. In this study we have tracked by mass spectrometry how palmitic acid from the adipocytes is released to media being later incorporated in different breast cancer cell lines (MDA-MB-231, SKBR3, BT474, MCF-7 and its resistant MCF-7 EPIR and MCF-7 TAXR). We have observed that different lines metabolize the palmitic acid in a different way and use their carbons in the synthesis of different new lipid families. Furthermore, we have observed that the lipid synthesis pattern varied according to the cell line. Surprisingly, the metabolic pattern of the resistant cells was more related to the TNBC cell line compared to their sensitive cell line MCF-7. These results allow us to determine a specific lipid pattern in different cell lines that later might be used in breast cancer diagnosis and to find a better treatment according to the cancer molecular type.

scholarly journals Antioxidant, anticancer and molecular docking activity of tulsi plant

2018 ◽  
Author(s):  
C.M. Noorjahan ◽  
T. Saranya
Keyword(s):  
Breast Cancer ◽  
Vero Cell ◽  
Cell Line ◽  
Cell Lines ◽  
Cancer Cell ◽  
Breast Cancer Cell ◽  
Cancer Cell Line ◽  
Ocimum Sanctum ◽  
Human Breast ◽  
Mcf 7

An investigation was carried out to study the antioxidant, anticancer and docking activities of medicinal plant, Tulsi – Ocimum sanctum. The results of antioxidant activity of Tulsi leaves extract showed that tulsi leaves has good free radical scavenging ability and IC50 value was found to be 54.23% at 500 µg/ml. The results of anticancer activity of Ocimum santum on normal VERO cell and MCF-7 cell line has showed good anticancer activity having the IC50 concentration at 51.1 ì|g/ml against MCF-7 cell lines – Human Breast cancer cell line thereby indicating that the percentage of cell viability increases with the increased concentration of Ocimum santum (Tulsi) whereas 24.4% cell viability was recorded in the normal VERO cell line. DNA laddering assay was performed on agarose gel electrophoresis. A clear fragmented DNA ladders were observed in tulsi treated MCF-7– Human Breast cancer cell lines. But the untreated normal VERO cell lines did not show any DNA fragmentation. Thereby confirms that Ocimum sanctum induced cell death on breast cancer cell line MCF-7 cancerous cell through apoptosis. Molecular docking was carried out (AutoDock tools), Docking simulations was performed using Lamarckian genetic algorithm of Solis and Wests local search method. Interaction between HDAC6 and Cirsilileon possessing binding energy showed +15.91kcal for interaction studies. It was found that most of the hydrogen bonding is with the residues TYR 76, TRP 35, SER 67, TYR 81, GLU 33, TYR 48, ILE 69 and MET 53 present in the binding pocket. The ligand was docked with the target protein, and the best docking poses were identified and the binding poses of the cirsilieon was shown. This act as the best docking poses shows how the ligand molecule fits into the binding region of the target protein.

Design, Synthesis and Cytotoxicity Evaluation of New 3, 5-Disubstituted-2-Thioxoimidazolidinones

2018 ◽  
Vol 18 (4) ◽  
pp. 573-582 ◽  
Author(s):  
Khaled R.A. Abdellatif ◽  
Mostafa M. Elbadawi ◽  
Mohammed T. Elsaady ◽  
Amer A. Abd El-Hafeez ◽  
Takashi Fujimura ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cell Line ◽  
Cell Lines ◽  
Cancer Cell ◽  
Topoisomerase I ◽  
Cancer Cell Line ◽  
Cytotoxic Agents ◽  
Dependent Manner ◽  
Human Lung Fibroblast ◽  
Mcf 7

Background: Some 2-thioxoimidazolidinones have been reported as anti-prostate and anti-breast cancer agents through their inhibitory activity on topoisomerase I that is considered as a potential chemotherapeutic target. Objective: A new series of 3,5-disubstituted-2-thioxoimidazolidinone derivatives 10a-f and their S-methyl analogs 11a-f were designed, synthesized and evaluated for cytotoxicity against human prostate cancer cell line (PC-3), human breast cancer cell line (MCF-7) and non-cancerous human lung fibroblast cell line (WI-38). </P><P> Results and Method: While compounds 10a-f showed a broad range of activities against PC-3 and MCF-7 cell lines (IC50 = 34.0 – 186.9 and 24.6 – 147.5 µM respectively), the S-methyl analogs 11a-f showed (IC50 = 22.7 – 198.5 and 16.9 – 188.2 µM respectively) in comparison with 5-fluorouracil (IC50 = 60.7 and 40.7 µM respectively). 11c (IC50 = 22.7 and 29.2 µM) and 11f (IC50 = 28.7 and 16.9 µM) were the most potent among all compounds against both PC-3 and MCF-7 respectively with no cytotoxicity against WI-38. Conclusion: The newly synthesized compounds showed good activity against PC-3 and MCF-7 cell lines in comparison with 5-fluorouracil. Compounds 11c and 11f bound with human topoisomerase I similar to its known inhibitors and significantly inhibited its DNA relaxation activity in a dose dependent manner which may rationalize their molecular mechanism as cytotoxic agents.

scholarly journals Histone Deacetylase Inhibitors and Microtubule Inhibitors Induce Apoptosis in Feline Luminal Mammary Carcinoma Cells

Animals ◽  
2021 ◽  
Vol 11 (2) ◽  
pp. 502
Author(s):  
Filipe Almeida ◽  
Andreia Gameiro ◽  
Jorge Correia ◽  
Fernando Ferreira
Keyword(s):  
Breast Cancer ◽  
Gene Expression ◽  
Cell Line ◽  
Cell Lines ◽  
Mammary Carcinoma ◽  
Human Breast Cancer ◽  
Histone Deacetylase Inhibitors ◽  
Trichostatin A ◽  
Human Breast ◽  
Antitumor Effects

Feline mammary carcinoma (FMC) is the third most common type of neoplasia in cats, sharing similar epidemiological features with human breast cancer. In humans, histone deacetylases (HDACs) play an important role in the regulation of gene expression, with HDAC inhibitors (HDACis) disrupting gene expression and leading to cell death. In parallel, microtubules inhibitors (MTIs) interfere with the polymerization of microtubules, leading to cell cycle arrest and apoptosis. Although HDACis and MTIs are used in human cancer patients, in cats, data is scarce. In this study, we evaluated the antitumor properties of six HDACis (CI-994, panobinostat, SAHA, SBHA, scriptaid, and trichostatin A) and four MTIs (colchicine, nocodazole, paclitaxel, and vinblastine) using three FMC cell lines (CAT-MT, FMCp, and FMCm), and compared with the human breast cancer cell line (SK-BR-3). HDACis and MTIs exhibited dose-dependent antitumor effects in FMC cell lines, and for all inhibitors, the IC50 values were determined, with one feline cell line showing reduced susceptibility (FMCm). Immunoblot analysis confirmed an increase in the acetylation status of core histone protein HDAC3 and flow cytometry showed that HDACis and MTIs lead to cellular apoptosis. Overall, our study uncovers HDACis and MTIs as promising anti-cancer agents to treat FMCs.

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