Essential oil loaded pectin/chitosan nanoparticles preparation and optimization via Box–Behnken design against MCF-7 breast cancer cell lines

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 Anticancer Activity of Cetraria Islandica (L.) Ach in Breast Cancer Cells Through Crosstalk of Ampk-α1 and Erk1/2 Signalling

Turkish Journal of Agriculture - Food Science and Technology ◽

10.24925/turjaf.v6i6.783-791.1940 ◽

2018 ◽

Vol 6 (6) ◽

pp. 783

Author(s):

Celal Güven ◽

Eylem Taskın ◽

Onder Yumtutas ◽

Leyla Turker Sener ◽

Yusuf Ozay ◽

...

Keyword(s):

Breast Cancer ◽

Cell Viability ◽

Cancer Cells ◽

Protein Level ◽

Breast Cancer Cells ◽

Caspase 3 ◽

Breast Cancer Cell Lines ◽

High Dose ◽

Protein Levels ◽

Mcf 7

In the present study, we aimed to evaluate the anticancer activities of Cetraria islandica (C.islandica) extracts on MCF-7 breast cancer cell lines. Cell viability, protein levels, apoptotic cells number, F-actin distribution were measured. Cell viability of MCF-7 breast cancer cells was found to be reduced in a dose-dependent manner.EC50 values of C.islandica on MCF-7 cells were found to be 9.2047 E-5 g/ml (cell amount) by using intelligence system. Expressions of p53, caspase 3 and Bcl-2, were shown to be elevated after low doses of extract and diminished after high dose treatments. PPAR- protein level was decreased, although AMP-activated kinases-α1 (AMPK-α1) protein level was increasedin its extract groups. ERK1/2 protein level was also elevated in its extract groups. 125 mg/ml of extract treated cells show a low decrease in actin filament density. MCF-7 cells with C.islandica treatment for 24 h increased the apoptotic cell percentage, though the cells-treated with C.islandica for 48 was high necrotic cells percentage. Consequently, the C.islandica extract treatment causes to elevate ERK1/2 and AMPK-α1 protein levels, resulting in PPAR- and then triggers the apoptosis by modulation caspase-3 and P53 protein levels. Therefore, C.islandica might be a good candidate for anticancer tissue, especially soft tissue tumours.

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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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Cytotoxic activity of crude saponins from Gaultheria trichophylla against human breast cancer cells MCF-7 and MDA-MB-468

Bangladesh Journal of Pharmacology ◽

10.3329/bjp.v10i2.22992 ◽

2015 ◽

Vol 10 (2) ◽

pp. 443

Author(s):

Fiaz Alam ◽

Qazi Najam us Saqib ◽

Abdul Waheed

Keyword(s):

Breast Cancer ◽

Cell Viability ◽

Crude Extract ◽

Human Breast Cancer ◽

Neutral Red ◽

Breast Cancer Cell Lines ◽

Dependent Manner ◽

Human Breast ◽

Uptake Assay ◽

Mcf 7

This study was conducted to evaluate Gaultheria trichophylla crude extract and respective saponins fraction against human breast cancer cell lines. In MTT assay, cell viability was inhibited by G. trichophylla crude extract (500 µg/mL) and saponins (200 µg/mL) in a dose dependent manner with maximum inhibition of (82% and 85%) and (71% and 42%) against MCF-7 and MDA MB-468, respectively. In neutral red uptake assay, the cell viability was inhibited by crude extract and saponins (100 µg/mL) in a similar manner with maximum inhibitions of (96% and 93%) and (87% and 61%) against MCF-7 and MDA MB-468, respectively, with respect to 91% and 93% inhibition by actinomycin-D (4 µM). The DAPI (4',6-diamidino-2-phenylindole) (10 µg/mL) staining of MCF-7 cells treated with crude saponins showed shrunken nuclei with apparent nuclear fragmentation indicating apoptosis and in contrast, MDA MB-468 showed necrosis mode of cell death. The study exhibited that the G. trichophylla provides new evidences to further explore this plant for the novel targets in anticancer drug development.

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Combinatorial Use of Chitosan Nanoparticles, Reversine, and Ionising Radiation on Breast Cancer Cells Associated with Mitosis Deregulation

Biomolecules ◽

10.3390/biom9050186 ◽

2019 ◽

Vol 9 (5) ◽

pp. 186 ◽

Cited By ~ 3

Author(s):

Sofia Piña Olmos ◽

Roberto Díaz Torres ◽

Eman Elbakrawy ◽

Louise Hughes ◽

Joseph Mckenna ◽

...

Keyword(s):

Breast Cancer ◽

Cell Viability ◽

Cancer Cells ◽

Breast Cancer Cells ◽

Spindle Assembly Checkpoint ◽

Genome Instability ◽

Chitosan Nanoparticles ◽

Genetic Material ◽

X Ray ◽

Before And After

Breast cancer is the most commonly occurring cancer in women worldwide and the second most common cancer overall. The development of new therapies to treat this devastating malignancy is needed urgently. Nanoparticles are one class of nanomaterial with multiple applications in medicine, ranging from their use as drug delivery systems and the promotion of changes in cell morphology to the control of gene transcription. Nanoparticles made of the natural polymer chitosan are easy to produce, have a very low immunogenic profile, and diffuse easily into cells. One hallmark feature of cancer, including breast tumours, is the genome instability caused by defects in the spindle-assembly checkpoint (SAC), the molecular signalling mechanism that ensures the timely and high-fidelity transmission of the genetic material to an offspring. In recent years, the use of nanoparticles to treat cancer cells has gained momentum. This is in part because nanoparticles made of different materials can sensitise cancer cells to chemotherapy and radiotherapy. These advances prompted us to study the potential sensitising effect of chitosan-based nanoparticles on breast cancer cells treated with reversine, which is a small molecule inhibitor of Mps1 and Aurora B that induces premature exit from mitosis, aneuploidy, and cell death, before and after exposure of the cancer cells to X-ray irradiation. Our measurements of metabolic activity as an indicator of cell viability, DNA damage by alkaline comet assay, and immunofluorescence using anti-P-H3 as a mitotic biomarker indicate that chitosan nanoparticles elicit cellular responses that affect mitosis and cell viability and can sensitise breast cancer cells to X-ray radiation (2Gy). We also show that such a sensitisation effect is not caused by direct damage to the DNA by the nanoparticles. Taken together, our data indicates that chitosan nanoparticles have potential application for the treatment of breast cancer as adjunct to radiotherapy.

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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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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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Regulation of cell cycle and cyclins by 16alpha-hydroxyestrone in MCF-7 breast cancer cells

Journal of Molecular Endocrinology ◽

10.1677/jme.0.0270293 ◽

2001 ◽

Vol 27 (3) ◽

pp. 293-307 ◽

Cited By ~ 13

Author(s):

JS Lewis ◽

TJ Thomas ◽

CM Klinge ◽

MA Gallo ◽

T Thomas

Keyword(s):

Breast Cancer ◽

Cell Cycle ◽

Dna Synthesis ◽

Cancer Cells ◽

Breast Cancer Cells ◽

Cell Cycle Progression ◽

Fold Increase ◽

Cycle Progression ◽

Synchronized Cells ◽

Mcf 7

It has been suggested that alterations in estradiol (E(2)) metabolism, resulting in increased production of 16alpha-hydroxyestrone (16alpha-OHE(1)), is associated with an increased risk of breast cancer. In the present study, we examined the effects of 16alpha-OHE(1)on DNA synthesis, cell cycle progression, and the expression of cell cycle regulatory genes in MCF-7 breast cancer cells. G(1) synchronized cells were treated with 1 to 25 nM 16alpha-OHE(1) for 24 and 48 h. [(3)H]Thymidine incorporation assay showed that 16alpha-OHE(1) caused an 8-fold increase in DNA synthesis compared with that of control cells, whereas E(2) caused a 4-fold increase. Flow cytometric analysis of cell cycle progression also demonstrated the potency of 16alpha-OHE(1) in stimulating cell growth. When G(1) synchronized cells were treated with 10 nM 16alpha-OHE(1) for 24 h, 62+/-3% of cells were in S phase compared with 14+/-3% and 52+/-2% of cells in the control and E(2)-treated groups respectively. In order to explore the role of 16alpha-OHE(1) in cell cycle regulation, we examined its effects on cyclins (D1, E, A, B1), cyclin dependent kinases (Cdk4, Cdk2), and retinoblastoma protein (pRB) using Western and Northern blot analysis. Treatment of cells with 10 nM 16alpha-OHE(1) resulted in 4- and 3-fold increases in cyclin D1 and cyclin A, respectively, at the protein level. There was also a significant increase in pRB phosphorylation and Cdk2 activation. In addition, transient transfection assay using an estrogen response element-driven luciferase reporter vector showed a 15-fold increase in estrogen receptor-mediated transactivation compared with control. These results show that 16alpha-OHE(1) is a potent estrogen capable of accelerating cell cycle kinetics and stimulating the expression of cell cycle regulatory proteins.

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Estrogen Withdrawal-Induced NF-κB Activity and Bcl-3 Expression in Breast Cancer Cells: Roles in Growth and Hormone Independence

Molecular and Cellular Biology ◽

10.1128/mcb.23.19.6887-6900.2003 ◽

2003 ◽

Vol 23 (19) ◽

pp. 6887-6900 ◽

Cited By ~ 75

Author(s):

M. A. Christine Pratt ◽

Tanya E. Bishop ◽

Dawn White ◽

Gordon Yasvinski ◽

Michel Ménard ◽

...

Keyword(s):

Breast Cancer ◽

Dna Binding ◽

Cancer Cells ◽

Breast Cancer Cells ◽

Breast Cancer Cell Lines ◽

Stable Form ◽

Estrogen Withdrawal ◽

Hormone Independence ◽

Mcf 7

ABSTRACT About one-third of breast cancers express a functional estrogen (β-estradiol [E2]) receptor (ER) and are initially dependent on E2 for growth and survival but eventually progress to hormone independence. We show here that ER+, E2-independent MCF-7/LCC1 cells derived from E2-dependent MCF-7 cells contain elevated basal NF-κB activity and elevated expression of the transcriptional coactivator Bcl-3 compared with the parental MCF-7 line. LCC1 NF-κB activity consists primarily of p50 dimers, although low levels of a p65/p50 complex are also present. The ER− breast cancer cell lines harbor abundant levels of both NF-κB complexes. In contrast, nuclear extracts from MCF-7 cells contain a significantly lower level of p50 and p65 than do LCC1 cells. Estrogen withdrawal increases both NF-κB DNA binding activity and expression of Bcl-3 in MCF-7 and LCC1 cells in vitro and in vivo. Tumors derived from MCF-7 cells ectopically expressing Bcl-3 remain E2 dependent but display a markedly higher tumor establishment and growth rate compared to controls. Expression of a stable form of IκBα in LCC1 cells severely reduced nuclear expression of p65 and the p65/p50 DNA binding heterodimer. Whereas LCC1 tumors in nude mice were stable or grew, LCC1(IκBα) tumors regressed after E2 withdrawal. Thus, both p50/Bcl-3- and p65/p50-associated NF-κB activities are activated early in progression and serve differential roles in growth and hormone independence, respectively. We propose that E2 withdrawal may initiate selection for hormone independence in breast cancer cells by activation of NF-κB and Bcl-3, which could then supplant E2 by providing both survival and growth signals.

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Modeling of antiproliferative effects of Salvia officinalis L. essential oil optimized using Box–Behnken design

10.21203/rs.3.rs-44076/v1 ◽

2020 ◽

Author(s):

Imen Kallel ◽

Ahmed Bayoudh ◽

Bochra Gargouri ◽

Lamia Khannous ◽

Asma Elaguel ◽

...

Keyword(s):

Essential Oil ◽

Cell Viability ◽

Cell Lines ◽

Human Cancer ◽

Salvia Officinalis ◽

Dependent Manner ◽

Box Behnken Design ◽

Cytotoxicity Activity ◽

Mcf 7

Abstract Background Salvia officinalis L. essential oil (SoEO) was mostly traditionally used to medicate various diseases as cancer. Then, the present work aims were: (1) to model the cytotoxicity effects of Salvia officinalis L. essential oil (SoEO) related to the human cancer cell lines kind (MCF-7 and HeLa) ; (2) to optimize the hydro-distillation extraction conditions of SoEO; and, (3) to determine the in vitro scavenging capacity of the free radicals DPPH•, NO•, ABTS+, and the ability to reduce Fe3+. Methods The cytotoxicity and anti-proliferative abilities were evaluated by measuring cell viability and then modeled. Two human cell lines: MCF-7 and HeLa were used. The optimization of SoEO extraction by hydro-distillation was carried out with Response Surface Methodology (RSM) using the Box–Behnken design Results The cytotoxicity activity against both tumor cell lines MCF-7 and HeLa was considerably important with IC50 = 3.125 and 8.920 µg/mL, respectively. All treated cell lines showed a significant reducing in cell viability in response to the increasing oil concentration. The relative behaviors of both cell lines under SoEO treatment were modeled. The obtained optimal extraction yield was Y = 1.85 g/100 g d.b. The main identified fractions were camphene (23.7%), α-thujone (19.62%), 1,8-cineole (10.6%), viridiflorol (5.9%), borneol (5.72%); β-thujone (5.4%); caryophyllene (3,83%). Also, SoEO was mostly able to scavenge DPPH• free radical, ABTS+ radical and hydrogen peroxide in an amount dependent manner (IC50 = 0.97, 0.279 and 0.05 mg/mL, respectively). Conclusion The present work provides a preliminary platform for further investigation of the possible mechanism of S. officinalis essential oils and their individual compounds in cytotoxic and antitumor activity.

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