Dihydroartemisinin-loaded Magnetic Nanoparticles for Enhanced Chemodynamic Therapy

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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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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ARTEMISININ MODULATING EFFECT ON HUMAN BREAST CANCER CELL LINES WITH DIFFERENT SENSITIVITY TO CYTOSTATICS

Experimental Oncology ◽

10.31768/2312-8852.2017.39(1):25-29 ◽

2017 ◽

Vol 39 (1) ◽

pp. 25-29 ◽

Cited By ~ 4

Author(s):

V F Chekhun ◽

N Yu Lukianova ◽

T Borikun ◽

T Zadvornyi ◽

A Mokhir

Keyword(s):

Breast Cancer ◽

Drug Resistance ◽

Cancer Cells ◽

Breast Cancer Cells ◽

Iron Homeostasis ◽

Chemotherapeutic Agents ◽

Fold Change ◽

Breast Cancer Cell Lines ◽

Cellular Iron ◽

Mcf 7

Aim: To explore effects of Artemisinin on a series of breast cancer cells with different sensitivity to typical cytotoxic drugs (doxorubicin — Dox; cisplatin — DDP) and to investigate possible artemisinin-induced modification of the mechanisms of drug resistance. Materials and Methods: The study was performed on wild-type breast cancer MCF-7 cell line (MCF-7/S) and its two sublines MCF-7/Dox and MCF-7/DDP resistant to Dox and DDP, respectively. The cells were treated with artemisinin and iron-containing magnetic fluid. The latter was added to modulate iron levels in the cells and explore its role in artemisinin-induced effects. The MTT assay was used to monitor cell viability, whereas changes of expression of selected proteins participating in regulation of cellular iron homeostasis were estimated using immunocytochemical methods. Finally, relative expression levels of miRNA-200b, -320a, and -34a were examined by using qRT-PCR. Results: Artemisinin affects mechanisms of the resistance of breast cancer cells towards both Dox and DDP at sub-toxic doses. The former drug induces changes of expression of iron-regulating proteins via different mechanisms, including epigenetic regulation. Particularly, the disturbances in ferritin heavy chain 1, lactoferrin, hepcidin (decrease) and ferroportin (increase) expression (р ≤ 0.05) were established. The most enhanced increase of miRNA expression under artemisinin influence were found for miRNA-200b in MCF-7/DDP cells (7.1 ± 0.98 fold change), miRNA-320a in MCF-7/Dox cells (2.9 ± 0.45 fold change) and miRNA-34a (1.7 ± 0.15 fold change) in MCF-7/S cells. It was observed that the sensitivity to artemisinin can be influenced by changing iron levels in cells. Conclusions: Artemisinin can modify iron metabolism of breast cancer cells by its cytotoxic effect, but also by inducing changes in expression of iron-regulating proteins and microRNAs (miRNAs), involved in their regulation. This modification affects the mechanisms that are implicated in drug-resistance, that makes artemisinin a perspective modulator of cell sensitivity towards chemotherapeutic agents in cancer treatment.

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Selective Effects of Thioridazine on Self-Renewal of Basal-Like Breast Cancer Cells

Scientific Reports ◽

10.1038/s41598-019-55145-3 ◽

2019 ◽

Vol 9 (1) ◽

Cited By ~ 1

Author(s):

Matthew Tegowski ◽

Cheng Fan ◽

Albert S. Baldwin

Keyword(s):

Breast Cancer ◽

Cancer Cells ◽

Cell Lines ◽

Cancer Cell ◽

Breast Cancer Cells ◽

Cell Types ◽

Breast Cancer Cell Lines ◽

Breast Cancers ◽

Self Renewal ◽

Basal Like Breast Cancer

AbstractSeveral recent publications demonstrated that DRD2-targeting antipsychotics such as thioridazine induce proliferation arrest and apoptosis in diverse cancer cell types including those derived from brain, lung, colon, and breast. While most studies show that 10–20 µM thioridazine leads to reduced proliferation or increased apoptosis, here we show that lower doses of thioridazine (1–2 µM) target the self-renewal of basal-like breast cancer cells, but not breast cancer cells of other subtypes. We also show that all breast cancer cell lines tested express DRD2 mRNA and protein, regardless of thioridazine sensitivity. Further, DRD2 stimulation with quinpirole, a DRD2 agonist, promotes self-renewal, even in cell lines in which thioridazine does not inhibit self-renewal. This suggests that DRD2 is capable of promoting self-renewal in these cell lines, but that it is not active. Further, we show that dopamine can be detected in human and mouse breast tumor samples. This observation suggests that dopamine receptors may be activated in breast cancers, and is the first time to our knowledge that dopamine has been directly detected in human breast tumors, which could inform future investigation into DRD2 as a therapeutic target for breast cancer.

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Effet radiosensibilisateur de l'acide linoléique conjugué chez les cellules cancéreuses du sein MCF-7 et MDA-MB-231

Canadian Journal of Physiology and Pharmacology ◽

10.1139/y04-003 ◽

2004 ◽

Vol 82 (2) ◽

pp. 94-102 ◽

Cited By ~ 1

Author(s):

Geneviève Drouin ◽

Annie Douillette ◽

Pierre Lacasse ◽

Benoit Paquette

Keyword(s):

Breast Cancer ◽

Linoleic Acid ◽

Cancer Cells ◽

Conjugated Linoleic Acid ◽

Breast Cancer Cells ◽

Fold Increase ◽

Breast Cancer Cell Lines ◽

Apoptotic Pathways ◽

Induced Apoptosis ◽

Mcf 7

Apoptotic pathways in breast cancer cells are frequently altered, reducing the efficiency of radiotherapy. Conjugated linoleic acid (CLA), known to trigger apoptosis, was tested as radiosensitizer in breast cancer cells MCF-7 and MDA-MB-231. The CLA-mix, made up of the isomers CLA-9cis 11trans and CLA-10trans 12cis, was compared to three purified isomers, i.e., the CLA-9cis 11cis, CLA-9cis 11trans, and CLA-10trans 12cis. Using the apoptotic marker YO-PRO®-1, the CLA-9cis 11cis at 50 µmol/L turned out to be the best apoptotic inducer leading to a 10-fold increase in MCF-7 cells and a 2,5-fold increase in MDA-MB-231 cells, comparatively to the CLA-mix. Contrary to previous studies on colorectal and prostate cancer cells, CLA-10trans 12cis does not lead to an apoptotic response on breast cancer cell lines MCF-7 and MDA-MB-231. Our results also suggest that the main components of the CLA-mix (CLA-9cis 11trans and CLA-10trans 12cis) are not involved in the induction of apoptosis in the breast cancer cells studied. A dose of 5 Gy did not induce apoptosis in MCF-7 and MDA-MB-231 cells. The addition of CLA-9cis 11cis or CLA-mix has allowed us to observe a radiation-induced apoptosis, with the CLA-9cis 11cis being about 8-fold better than the CLA-mix. CLA-9cis 11cis turned out to be the best radiosensitizer, although the isomers CLA-9cis 11trans and CLA-10trans 12cis have also reduced the cell survival following irradiation, but using a mechanism not related to apoptosis. In conclusion, the radiosensitizing property of CLA-9cis 11cis supports its potential as an agent to improve radiotherapy against breast carcinoma.Key words: breast cancer, conjugated linoleic acid (CLA), radiotherapy, apoptosis.

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The Role of Aryl Hydrocarbon Receptor and Crosstalk with Estrogen Receptor in Response of Breast Cancer Cells to the Novel Antitumor Agents Benzothiazoles and Aminoflavone

International Journal of Breast Cancer ◽

10.4061/2011/923250 ◽

2011 ◽

Vol 2011 ◽

pp. 1-9 ◽

Cited By ~ 23

Author(s):

Mariana A. Callero ◽

Andrea I. Loaiza-Pérez

Keyword(s):

Breast Cancer ◽

Estrogen Receptor ◽

Aryl Hydrocarbon Receptor ◽

Cancer Cells ◽

Breast Cancer Cells ◽

Antitumor Agents ◽

Breast Cancers ◽

Nude Mouse Model ◽

Aryl Hydrocarbon ◽

Mcf 7

Many estrogen-receptor- (ER-) expressing breast cancers become refractory to ER-based therapies. New antitumor drugs like aminoflavone (AF) and benzothiazoles (Bzs) have been developed and have exquisite antitumor activity in ER+MCF-7 and T47D cells and in a MCF-7 nude mouse model. ER(−) breast cancer cells like MDA-MB-231 are less susceptible. We previously found in MCF-7 cells that these drugs activate the aryl hydrocarbon receptor (AhR) via translocation to the nucleus, induction of AhR-specific DNA binding activity, and expression of CYP1A1, whose transcription is controlled by the AhR-ARNT transcription factor. CYP1A1 metabolizes AF and Bz to a species which directly or after further metabolism damages DNA. In contrast an AhR-deficient variant of MCF-7 or cells with predominantly nuclear AhR expression, such as MDA-MB 231, are resistant. Thus, these drugs, unlike other neoplastic agents, require AhR-mediated signaling to cause DNA damage. This is a new treatment strategy for breast cancers with intact AhR signaling.

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A Combination of an Antimitotic and a Bromodomain 4 Inhibitor Synergistically Inhibits the Metastatic MDA-MB-231 Breast Cancer Cell Line

BioMed Research International ◽

10.1155/2019/1850462 ◽

2019 ◽

Vol 2019 ◽

pp. 1-13 ◽

Cited By ~ 1

Author(s):

Thandi Mqoco ◽

André Stander ◽

Anna-Mart Engelbrecht ◽

Anna M Joubert

Keyword(s):

Breast Cancer ◽

Cancer Cells ◽

Cell Line ◽

Cancer Cell ◽

Breast Cancer Cell ◽

Breast Cancer Cells ◽

Chemotherapeutic Agents ◽

Breast Cancer Cell Lines ◽

Mcf 7

Current chemotherapeutic agents have many side effects and are toxic to normal cells, providing impetus to identify agents that can effectively eliminate tumorigenic cells without damaging healthy cells. The aim of this study was to examine whether combining a novel BRD4 inhibitor, ITH-47, with the antimitotic estradiol analogue, ESE-15-ol, would have a synergistic effect on inhibiting the growth of two different breast cancer cell lines in vitro. Our docking and molecular dynamics studies showed that compared to JQ1, ITH-47 showed a similar binding mode with hydrogen bonds forming between the ligand nitrogens of the pyrazole, ASN99, and water of the BRD4 protein. Data from cell growth studies revealed that the GI50 of ITH-47 and ESE-15-ol after 48 hours of exposure was determined to be 15 μM and 70 nM, respectively, in metastatic MDA-MB-231 breast cancer cells. In tumorigenic MCF-7 breast cancer cells, the GI50 of ITH-47 and ESE-15-ol was 75 μM and 60 nM, respectively, after 48 hours of exposure. Furthermore, the combination of 7.5 μM and 14 nM of ITH-47 and ESE-15-ol, respectively, resulted in 50% growth inhibition of MDA-MB-231 cells resulting in a synergistic combination index (CI) of 0.7. Flow cytometry studies revealed that, compared to the control, combination-treated MDA-MB-231 cells had significantly more cells present in the sub-G1 phase and the combination treatment induced apoptosis in the MDA-MB-231 cells. Compared to vehicle-treated cells, the combination-treated cells showed decreased levels of the BRD4, as well as c-Myc protein after 48 hours of exposure. In combination, the selective BRD4 inhibitor, ITH-47, and ESE-15-ol synergistically inhibited the growth of MDA-MB-231 breast cancer cells, but not of the MCF-7 cell line. This study provides evidence that resistance to BRD4 inhibitors may be overcome by combining inhibitors with other compounds, which may have treatment potential for hormone-independent breast cancers.

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Studies on Multifunctional Effect of All-Trans Retinoic Acid (ATRA) on Matrix Metalloproteinase-2 (MMP-2) and Its Regulatory Molecules in Human Breast Cancer Cells (MCF-7)

Journal of Oncology ◽

10.1155/2009/627840 ◽

2009 ◽

Vol 2009 ◽

pp. 1-13 ◽

Cited By ~ 24

Author(s):

Anindita Dutta ◽

Triparna Sen ◽

Aniruddha Banerji ◽

Shamik Das ◽

Amitava Chatterjee

Keyword(s):

Breast Cancer ◽

Cancer Cells ◽

Human Breast Cancer ◽

Breast Cancer Cells ◽

Gelatin Zymography ◽

Inhibitory Effect ◽

Human Breast Cancer Cells ◽

Human Breast ◽

Atra Treatment ◽

Mcf 7

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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Methotrexate-conjugated L-lysine coated iron oxide magnetic nanoparticles for inhibition of MCF-7 breast cancer cells

Drug Development and Industrial Pharmacy ◽

10.1080/03639045.2017.1417422 ◽

2017 ◽

Vol 44 (6) ◽

pp. 886-894 ◽

Cited By ~ 43

Author(s):

Hamed Nosrati ◽

Marziyeh Salehiabar ◽

Soodabeh Davaran ◽

Hossein Danafar ◽

Hamidreza Kheiri Manjili

Keyword(s):

Breast Cancer ◽

Iron Oxide ◽

Magnetic Nanoparticles ◽

Cancer Cells ◽

Breast Cancer Cells ◽

Iron Oxide Magnetic Nanoparticles ◽

Mcf 7

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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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Osteoblast-conditioned medium promotes proliferation and sensitizes breast cancer cells to imatinib treatment

Endocrine Related Cancer ◽

10.1677/erc.1.01307 ◽

2007 ◽

Vol 14 (1) ◽

pp. 61-72 ◽

Cited By ~ 13

Author(s):

Marina Brama ◽

Sabrina Basciani ◽

Sara Cherubini ◽

Stefania Mariani ◽

Silvia Migliaccio ◽

...

Keyword(s):

Breast Cancer ◽

Tyrosine Kinase ◽

Cancer Cells ◽

Conditioned Medium ◽

Human Breast Cancer ◽

Breast Cancer Cells ◽

Breast Cancer Cell Lines ◽

Imatinib Treatment ◽

Human Breast ◽

Mcf 7

Inhibition of platelet-derived growth factor receptor (PDGFR) signaling restricts the growth of human breast cancer in the bone of nude mice. We hypothesized that osteoblast-secreted substances may alter the response capacity of breast cancer cells to the PDGFRs tyrosine kinase inhibitor imatinib mesylate. We found that osteoblast-conditioned medium (OCM) increases the proliferation rate of the estrogen receptor negative (ER−) MDA-MB-231 and of the ER+ MCF-7 human breast cancer cell lines and the growth-promoting effect on ER+ cells is independent from estrogen. OCM significantly improved the dose- and the time-dependent sensitivity of the tumor cells to the anti-proliferative effect of imatinib. We also found that MDA-MB-231 and MCF-7 cells express the two PDGFRs subtypes, PDGFR-α and PDGFR-β, and OCM treatment increases the expression of the PDGFRs. Furthermore, imatinib inhibited the phosphorylation rate of its target tyrosine kinase receptors. We conclude that bone microenvironment, through osteoblast-secreted substances may cause estrogen-independent proliferation of breast cancer cells by a mechanism mediated by the induction of PDGFRs expression. The enhanced sensitivity of OCM-treated breast cancer cells to imatinib would justify investigation on the efficacy of imatinib in bone breast cancer metastasis.

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