Inhibitory effect of hydroxyflutamide plus tamoxifen on oestradiol-induced growth of MCF-7 breast cancer cells

Background. Vitamin A derivative all-trans retinoic acid (ATRA) is considered as a potent chemotherapeutic drug for its capability of regulating cell growth and differentiation. We studied the effect of ATRA on MMP-2 in MCF-7, human breast cancer cells, and the probable signaling pathways which are affected by ATRA on regulating pro-MMP-2 activity and expression.Methods. Gelatin zymography, RT-PCR, ELISA, Western blot, Immunoprecipitation, and Cell adhesion assay are used.Results. Gelatin zymography showed that ATRA caused a dose-dependent inhibition of pro-MMP-2 activity. ATRA treatment downregulates the expression of MT1-MMP, EMMPRIN, FAK, NF-kB, and p-ERK. However, expression of E-cadherin, RAR, and CRABP increased upon ATRA treatment. Binding of cells to extra cellular matrix (ECM) protein fibronectin reduced significantly after ATRA treatment.Conclusions. The experimental findings clearly showed the inhibition of MMP-2 activity upon ATRA treatment. This inhibitory effect of ATRA on MMP-2 activity in human breast cancer cells (MCF-7) may result due to its inhibitory effect on MT1-MMP, EMMPRIN, and upregulation of TIMP-2. This study is focused on the effect of ATRA on MMP, MMP-integrin-E-cadherin interrelationship, and also the effect of the drug on different signaling molecules which may involve in the progression of malignant tumor development.

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Overexpression of wild-type p53 gene renders MCF-7 breast cancer cells more sensitive to the antiproliferative effect of progesterone

Journal of Endocrinology ◽

10.1677/joe.0.1790055 ◽

2003 ◽

Vol 179 (1) ◽

pp. 55-62 ◽

Cited By ~ 25

Author(s):

M Alkhalaf ◽

AM El-Mowafy

Keyword(s):

Breast Cancer ◽

Cell Growth ◽

Growth Inhibition ◽

Cancer Cells ◽

Breast Cancer Cells ◽

P53 Protein ◽

P53 Gene ◽

Inhibitory Effect ◽

Antiproliferative Effect ◽

Mcf 7

We have recently shown that growth inhibition of breast cancer cells by progesterone is due to the induction of cell differentiation, but not apoptosis. Because the tumor suppressor protein p53 plays a central role in normal cell growth and in tumor suppression, we have examined the effect of progesterone on the levels of this protein in MCF-7 cells. We show here that the antiproliferative effect of progesterone is accompanied with down-regulation of endogenous p53 protein. To study the effect of progesterone on cell growth in the presence of normal levels of p53 protein, we used transient transfection to overexpress p53 protein. MCF-7 cells were transfected with a p53 expressing vector that contains p53 human cDNA under the control of a cytomegalovirus promoter. Cell growth, cell viability, and apoptosis were analyzed in the transfected cells after six days of exposure to 100 nM progesterone. We show here that progesterone significantly enhances growth inhibition and apoptosis in MCF-7 cells overexpressing p53, but not in cells transfected with the control vector. These data suggest that re-establishing p53 function in MCF-7 breast cancer cells renders them more sensitive to the growth inhibitory effect of progesterone.

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Effects of BET Inhibitor JQ1 and Interleukin-6 on Breast Cancer Cells

10.21203/rs.3.rs-1143331/v1 ◽

2021 ◽

Author(s):

Atefeh Sharif Hoseini ◽

Masoud Heshmati ◽

Amin Soltani ◽

Hedayatollah Shirzad ◽

Morteza Sedehi ◽

...

Keyword(s):

Breast Cancer ◽

Cancer Cells ◽

Breast Cancer Cells ◽

Therapeutic Targets ◽

Surface Expression ◽

Inhibitory Effect ◽

Dependent Manner ◽

Breast Cancers ◽

Bet Inhibitors ◽

Mcf 7

Abstract Bromodomain and extra-terminal (BET) proteins are recognized acetylated lysine of histone 4 and act as scaffolds to recruit many other proteins to promoters and at enhancers of active genes, especially at the super-enhancers of key genes, driving the transcription process and have been identified as potential therapeutic targets in breast cancer. However, the efficacy of BET inhibitors such as JQ1 in breast cancer therapy is impeded by IL-6 through an as yet defined mechanism. We investigated the interplay between IL-6 and JQ1 in MCF-7 and MDA-MB-231 human breast cancer cells. Here we demonstrate that the efficacy of JQ1 on the inhibition of cell growth and apoptosis was stronger in MDA-MB-231 cells than in MCF-7 cells. Further, MCF-7 cells, but not MDA-MB-231 cells, exhibited increased expression of CXCR4 following IL-6 treatment. JQ1 significantly reduced CXCR4 surface expression in both cell lines and diminished the effects of IL-6 pre-treatment on MCF-7 cells. While IL-6 suppressed the extension of breast cancer stem cells (BCSCs) in MCF-7 cells, JQ1 impeded its inhibitory effect. In addition, in MCF-7 cells JQ1 increased the number of senescent cells in a time-dependent manner. Analysis of gene expression indicated that JQ1 and IL-6 synergistically increase SNAIL expression and decrease c-MYC expression in MCF-7 cells. So, the BET proteins are promising, novel therapeutic targets in late-stage breast cancers.

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Dihydroartemisinin-loaded Magnetic Nanoparticles for Enhanced Chemodynamic Therapy

10.1101/2019.12.20.885400 ◽

2019 ◽

Author(s):

Shengdi Guo ◽

Xianxian Yao ◽

Qin Jiang ◽

Kuang Wang ◽

Yuanying Zhang ◽

...

Keyword(s):

Breast Cancer ◽

Magnetic Nanoparticles ◽

Cancer Cells ◽

Therapeutic Effect ◽

Breast Cancer Cells ◽

Inhibitory Effect ◽

Breast Cancer Cell Lines ◽

Breast Cancers ◽

Ferrous Ions ◽

Mcf 7

AbstractRecently, chemodynamic therapy (CDT) has represented a new approach for cancer treatment with low toxicity and side effects. Nonetheless, it has been a challenge to improve the therapeutic effect through increasing the amount of reactive oxygen species (ROS). Herein, we increased the amount of ROS agents in the Fenton-like reaction by loading dihydroartemisinin (DHA) which was an artemisinin (ART) derivative containing peroxide groups, into magnetic nanoparticles (MNP), thereby improving the therapeutic effect of CDT. Blank MNP were almost non-cytotoxic, whereas three MNP loading ART-based drugs, MNP-ART, MNP-DHA, and MNP-artesunate (MNP-AS), all showed significant killing effect on breast cancer cells (MCF-7 cells), in which MNP-DHA were the most potent. What’s more, the MNP-DHA showed high toxicity to drug-resistant breast cancer cells (MCF-7/ADR cells), demonstrating its ability to overcome multidrug resistance (MDR). The study revealed that MNP could produce ferrous ions under the acidic condition of tumor microenvironment, which catalyzed DHA to produce large amounts of ROS, leading to cell death. Further experiments also showed that the MNP-DHA had significant inhibitory effect on another two aggressive breast cancer cell lines (MDA-MB-231 and MDA-MB-453 cells), which indicated that the great potential of MNP-DHA for the treatment of intractable breast cancers.

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Inhibitory effect of Rhus verniciflua Stokes extract in MCF-7 human breast cancer cells

Herbal Formula Science ◽

10.14374/hfs.2016.24.4.283 ◽

2016 ◽

Vol 24 (4) ◽

pp. 283-288 ◽

Cited By ~ 1

Author(s):

Min Sung Kim ◽

Won Gun An ◽

Jang Cheon Lee

Keyword(s):

Breast Cancer ◽

Cancer Cells ◽

Human Breast Cancer ◽

Breast Cancer Cells ◽

Inhibitory Effect ◽

Human Breast Cancer Cells ◽

Human Breast ◽

Rhus Verniciflua Stokes ◽

Rhus Verniciflua ◽

Mcf 7

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Lidocaine Inhibits Breast Cancer Cell Proliferation and Induces Cell Apoptosis via Regulating MEK/ERK and PI3K/AKT Signalling Pathways

10.21203/rs.3.rs-617189/v1 ◽

2021 ◽

Author(s):

Xu Wang ◽

Shi-Hang Xi ◽

Qin Li ◽

ting han

Keyword(s):

Breast Cancer ◽

Cell Proliferation ◽

Cancer Cells ◽

Breast Cancer Cells ◽

Flow Cytometric Analysis ◽

Inhibitory Effect ◽

Potential Candidate ◽

Protein Levels ◽

M Phase ◽

Mcf 7

Abstract Background: Lidocaine is a commonly used local anesthetic in clinic, which is mainly used for anesthesia and analgesia. Lidocaine has been recently found to have an inhibitory effect on a variety of cancers.Materials and Methods: We used MTT assay and cell proliferation assay to detect the inhibition of lidocaine on proliferation of MCF-7 and MDA-MB-231 breast cancer cells. Flow cytometric analysis was used to detect cell cycle and apoptosis. Western blot was used to detect protein levels of cyclin-dependent kinase 1(CDK1) ,cyclinB1, BCL2, BCL-XL, p62, LC3B, p-ERK,p-AKT, ERK and AKT.Results: Lidocaine inhibited the proliferation of MCF-7 and MDA-MB-231 breast cancer cells, increased the percentage of G2 / M phase cells , apoptosis and autophagy by reducing the mRNA of CDK1 and cyclinB1, decreasing protein levels of CDK1,cyclinB1,BCL2, BCL-XL, p62, p-ERK and p-AKT protein, and increasing LC3B-II/LC3B-I protein levels.Conclusion: Lidocaine may be a potential candidate for treatment of breast cancer.

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Abstract P005: GRK4 Inhibitors Suppress Breast Cancer Cell Growth And Potentiate The Inhibitory Effect Of Dopaminergic D 1 Receptor Agonist SKF38393

Hypertension ◽

10.1161/hyp.76.suppl_1.p005 ◽

2020 ◽

Vol 76 (Suppl_1) ◽

Author(s):

Wei Yue ◽

Jiping Wang ◽

John J Gildea ◽

Peng Xu ◽

Stephen Marshall ◽

...

Keyword(s):

Breast Cancer ◽

Growth Inhibition ◽

Cancer Cells ◽

Sodium Excretion ◽

Breast Cancer Cells ◽

Inhibitory Effect ◽

Cell Number ◽

Compound A ◽

Compound C ◽

Mcf 7

The renal dopaminergic D 1 receptor (D 1 R) regulates sodium excretion which is terminated by phosphorylation by G protein-coupled receptor kinases 4 (GRK4). GRK4 gene variants are associated with increased GRK4 activity and reduced sodium excretion resulting in hypertension. Breast cancer incidence is higher in hypertensive women. We found that GRK4 is a potential molecule linking these two diseases. We hypothesized that GRK4 inhibitors would be beneficial to patients with hypertension and breast cancer. Three potential GRK4 inhibitors (compounds A, B, and C) were tested for their effect on the growth of breast cancer cells MDA-MB-468, MCF-7, and benign mammary epithelial cells MCF-10A controls. These cell lines had high, low, and no GRK4 expression respectively. Growth of MDA-MB-468 and MCF-7 cells was effectively inhibited by compound C with IC 50 16.8±1.9 nM (n=2). MCF-10A cells were relatively resistant to compound C with IC 50 49.3±4.0 nM (n=3) that is significantly higher than the cancer cells (p<0.001). Compound B was the least effective inhibitor in all three cell lines (IC 50 was 1.5-2.3 μM). Growth inhibition of compound A was similar in MCF-7 and MCF-10A cells but less effective in MDA-MB-468 cells indicating GRK4 inhibition may not be the only target for growth inhibition of this compound. It has been reported that D 1 R agonists inhibit growth of breast cancer cells. We hypothesized that blockade of GRK4 would increase sensitivity of breast cancer cells to the inhibitory effect of a D 1 R agonist. In MDA-MB-468 cells, SKF38393 (SKF) at 20 μM caused a 36% reduction in cell number (from 276.7±0.47E4 to 177.7±4.33E4). Compound C alone reduced cell number by 37% (172.4±0.04E4, 5 nM) and 51% (136.3±7.87E4, 10 nM) respectively. Combination treatment induced more reduction in cell number, 63% (100.4±5.54E4, 5 nM) and 84% (44.1±12.7E4, 10 nM). Similarly, Compound A also enhanced the inhibitory effect of SKF. A left-shift of the SKF dose-response curve in GKR4 knock-down MDA-MB-468 cells confirmed that inhibition of GRK4 increases sensitivity of breast cancer cells to SKF. Our preliminary results suggest that targeting GRK4 with compound C and a dopaminergic agonist could be a novel strategy for breast cancer therapy especially for the patients with hypertension.

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The NF-κB Signaling and Wnt/β-catenin Signaling in MCF-7 Breast Cancer Cells in Response to Bioactive Components from Mushroom Antrodia Camphorata

The American Journal of Chinese Medicine ◽

10.1142/s0192415x21500117 ◽

2020 ◽

pp. 1-17

Author(s):

Ting-Chun Lin ◽

Alison Germagian ◽

Zhenhua Liu

Keyword(s):

Breast Cancer ◽

Cancer Cells ◽

Breast Cancer Cells ◽

Inhibitory Effect ◽

Luciferase Assay ◽

Bioactive Components ◽

Antrodia Camphorata ◽

Anticancer Properties ◽

Anti Inflammatory ◽

Mcf 7

Breast cancer is the leading cancer, accounting for approximately 15% cancer deaths in women worldwide. This study investigated the anti-inflammation and anticancer properties of two bioactive components from Antrodia camphorata(AC), a rare medicinal mushroom natively grown in Taiwan and commonly used in Chinese traditional medicine. The anti-inflammatory and antitumorigenic functions of Antroquinonol (AQ) and 4-Acetylantroquinonol B (4-AAQB) from AC were examined on breast cancer cell line MCF-7 with/without TNF-[Formula: see text] stimulation. Among nine inflammatory mediators (IL6, IL10, IL1[Formula: see text], IFN[Formula: see text], PTGS2, TGF[Formula: see text]1, TNF-[Formula: see text], CCL2 andCSF1) examined, AQ inhibited two of them (IL-10 and PTGS2), while 4-AAQB inhibited three of them (IL-10, PTGS2 andTNF-[Formula: see text] ([Formula: see text]¡ 0.05). TNF-[Formula: see text] stimulated expressions of five mediators (IL6, IL10, IFN[Formula: see text], PTGS2, and CCL2), and AQ and 4-AAQB inhibited IL6 elevation ([Formula: see text]¡ 0.05). Both components inhibited aromatase expression with/without TNF-[Formula: see text] stimulation, with 4-AAQB to be more effective ([Formula: see text]¡ 0.05). For immune checkpoint CD47, both components inhibited CD47 expression ([Formula: see text]¡ 0.05), but it did not respond to TNF-[Formula: see text] stimulation. For Wnt/[Formula: see text]- catenin signaling downstream genes (CCND1, C-MYC and AXIN2), both components have significant or marginal inhibitory effect on C-MYC in the condition with/without TNF-[Formula: see text] stimulation. The luciferase assay demonstrated that both components exhibited inhibitory effect on NF-[Formula: see text]B signaling and Wnt/[Formula: see text]-catenin signaling in the condition without TNF-[Formula: see text] stimulation. In conclusion, our results displayed an overall pattern that AQ and 4-AAQB possess potential anti-inflammatory and antitumorigenic functions in MCF-7 breast cancer cells and warranted further in vivo pre-clinical and clinical studies to explore their anticancer properties.

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