scholarly journals The effects and possible mechanism of action of apolipoprotein M on the growth of breast cancer cells

2021 ◽  
Author(s):  
Ying Zhou ◽  
Shuang Yao ◽  
Miaomei Yu ◽  
Jiang Wei ◽  
Qi Fang ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Mechanism Of Action ◽  
Breast Cancer Cells ◽  
Animal Experiments ◽  
Breast Cancer Cell Lines ◽  
Apolipoprotein M ◽  
Main Pathway ◽  
The Difference ◽  
Mcf 7

Abstract Background: To investigate the effects and mechanism of action of apolipoprotein M (ApoM) on the growth of breast cancer (BC) cells.Methods and Results: Bioinformatics, cell experiments and animal experiments were used to verify the effect of ApoM on breast cancer cell lines and breast tumor growth in vivo. ApoM expression was significantly reduced in BC tissues, and patients with lower ApoM mRNA expression had a poorer prognosis (P<0.0001). Besides, ApoM can partially inhibit the proliferative, migratory and invasive processes of BC cells. In vivo, the difference between ApoM-OE and NC groups was no significant. The level of vitamin D receptor (VDR) protein in MDA-MB-231 cells was increased by overexpression of ApoM (P<0.05), while in MCF-7 cells, VDR levels decreased (P<0.05).Conclusions: ApoM can partially inhibit the growth of BC cells. VDR may play a role, but is not the main pathway.

The synergistic effect between celecoxib and luteolin and dependence on estrogen receptor in human breast cancer cells.

2015 ◽  
Vol 33 (28_suppl) ◽  
pp. 135-135
Author(s):  
Ye-Won Jeon ◽  
Youngjin Suh
Keyword(s):  
Breast Cancer ◽  
Cancer Cells ◽  
Cell Lines ◽  
Combination Treatment ◽  
Breast Cancer Cells ◽  
Synergistic Effects ◽  
Breast Cancer Cell Lines ◽  
Human Breast ◽  
Mcf 7

135 Background: The anti-cancer effects of celecoxib and luteolin are well known. Although our previous study demonstrated that the combination of celecoxib and luteolin synergistically inhibits breast tumor growth compared with each of the treatments alone, we did not uncover the molecular mechanisms of these effects. The aims of our present study were to compare the effects of a celecoxib and luteolin combination treatment in four different human breast cell lines and to determine the mechanisms of action in vitro and in vivo. Methods: Using MCF-7, MCF7/HER18, MDA-MB-231 and SkBr3 human breast cancer cells, proliferation assay, apoptosis assay, inhibition assay with MEK and PI3K inhibitor in addition to western blotting and xenograft study after treatment with celecoxib and luteolin. Results: The synergistic effects of a celecoxib and luteolin combination treatment yielded significantly greater cell growth inhibition in all four breast cancer cell lines compared with the single agents alone. In particular, combined celecoxib and luteolin treatment significantly decreased the growth of MDA-MB-231 cancer cells in vivo compared with either agent alone. The celecoxib and luteolin combination treatment induced synergistic effects via Akt inactivation and extracellular signal-regulated kinase (ERK) signaling inhibition in MCF-7 and MCF7/HER18 cells and via Akt inactivation and ERK signaling activation in MDA-MB-231 and SkBr3 cells. Conclusions: These results demonstrate the synergistic anti-tumor effect of the celecoxib and luteolin combination treatment in different four breast cancer cell lines, thus introducing the possibility of this combination as a new treatment modality.

scholarly journals Salicin a promising ER, PR and HER2 binding molecule proving lethal against Hormone + and triple negative breast cancer cells

2021 ◽  
Vol 12 (1) ◽  
pp. 73-83
Author(s):  
Mrudul Pravinbhai Vekaria ◽  
Pravin Tirgar
Keyword(s):  
Breast Cancer ◽  
Cancer Cells ◽  
Triple Negative Breast Cancer ◽  
Mechanism Of Action ◽  
Breast Cancer Cells ◽  
Triple Negative ◽  
Minimum Energy ◽  
Good Choice ◽  
Breast Cancer Cell Lines ◽  
Mcf 7

Therapeutics against breast cancer is a major research field, due to inefficiency or partial efficiency of existing therapeutics.  An urge to discover better therapeutics always persists. Our objective is to study salicin against breast cancer cells, in order to find its therapeutic properties. To study the effect of salicin on breast cancer cells, we performed MTT assay on MCF-7 (hormone positive) and MDA-MB-231 (triple negative) breast cancer cell lines, we did brine shrimp lethality test (BSLT) assay to see the lethal effects of salicin. By the help of bioinformatics we tried to locate the targets that delineate salicin activity. Salicin was docked with estrogen receptor (ER), progesterone receptor (PR) and Human epidermal growth factor receptor 2 (HER2) to study its binding efficiency and possible targets of salicin. Salicin remarkably reduces cell viability both in MCF-7 and MDA-MB-231, along with being lethal to brine shrimps. These results together opine that salicin can be an effective therapeutics against breast cancer cells. The mechanism of action of salicin is probably through ER, PR and HER2 receptors because it can efficiently bind these receptors with minimum energy required for binding. This explains that salicin can easily bind to these receptors. These results together opine that salicin can be an effective therapeutics against breast cancer cells. The mechanism of action of salicin is probably through ER, PR and HER2 receptors because it can efficiently bind these receptors with minimum binding energy. ER, PR and HER2 are major reasons behind the disease pathogenicity depending on the type of breast cancer. According to our results salicin may either induce apoptosis or reduce cellular mitosis both via P53 dependent and independent pathway, which makes salicin a good choice of both hormone positive and negative breast cancer cells. 

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 ◽  
Mcf 7

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.

In vitro evaluation of estrogenic, antiestrogenic and antitumor effects of amentoflavone

2021 ◽  
pp. 096032712199945
Author(s):  
AT Aliyev ◽  
S Ozcan-Sezer ◽  
A Akdemir ◽  
H Gurer-Orhan
Keyword(s):  
Breast Cancer ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Antitumor Effects ◽  
Antiestrogenic Activity ◽  
Er Positive ◽  
In Vivo Effects ◽  
Mcf 7

Apigenin, a flavonoid, is reported to act as an estrogen receptor (ER) agonist and inhibit aromatase enzyme. However, amentoflavone, a biflavonoid bearing two apigenin molecules, has not been evaluated for its endocrine modulatory effects. Besides, it is highly consumed by young people to build muscles, enhance mood and lose weight. In the present study, apigenin was used as a reference molecule and ER mediated as well as ER-independent estrogenic/antiestrogenic activity of amentoflavone was investigated. Antitumor activity of amentoflavone was also investigated in both ER positive (MCF-7 BUS) and triple-negative (MDA-MB-231) breast cancer cells and its cytotoxicity was evaluated in human breast epithelial cells (MCF-10A). Our data confirmed ER agonist, aromatase inhibitory and cytotoxic effects of apigenin in breast cancer cells, where no ER mediated estrogenic effect and physiologically irrelevant, slight, aromatase inhibition was found for amentoflavone. Although selective cytotoxicity of amentoflavone was found in MCF-7 BUS cells, it does not seem to be an alternative to the present cytotoxic drugs. Therefore, neither an adverse effect, mediated by an estrogenic/antiestrogenic effect of amentoflavone nor a therapeutical benefit would be expected from amentoflavone. Further studies could be performed to investigate its in vivo effects.

scholarly journals Tioconazole and Chloroquine Act Synergistically to Combat Doxorubicin-Induced Toxicity via Inactivation of PI3K/AKT/mTOR Signaling Mediated ROS-Dependent Apoptosis and Autophagic Flux Inhibition in MCF-7 Breast Cancer Cells

2021 ◽  
Vol 14 (3) ◽  
pp. 254
Author(s):  
Afnan H. El-Gowily ◽  
Samah A. Loutfy ◽  
Ehab M. M. Ali ◽  
Tarek M. Mohamed ◽  
Mohammed A. Mansour
Keyword(s):  
Breast Cancer ◽  
Combination Therapy ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Mtor Pathway ◽  
Tumor Growth Inhibition ◽  
Autophagic Flux ◽  
Ki 67 ◽  
Mcf 7

Cancer is a complex devastating disease with enormous treatment challenges, including chemo- and radiotherapeutic resistance. Combination therapy demonstrated a promising strategy to target hard-to-treat cancers and sensitize cancer cells to conventional anti-cancer drugs such as doxorubicin. This study aimed to establish molecular profiling and therapeutic efficacy assessment of chloroquine and/or tioconazole (TIC) combination with doxorubicin (DOX) as anew combination model in MCF-7 breast cancer. The drugs are tested against apoptotic/autophagic pathways and related redox status. Molecular docking revealed that chloroquine (CQ) and TIC could be potential PI3K and ATG4B pathway inhibitors. Combination therapy significantly inhibited cancer cell viability, PI3K/AkT/mTOR pathway, and tumor-supporting autophagic flux, however, induced apoptotic pathways and altered nuclear genotoxic feature. Our data revealed that the combination cocktail therapy markedly inhibited tumor proliferation marker (KI-67) and cell growth, along with the accumulation of autophagosomes and elevation of LC3-II and p62 levels indicated autophagic flux blockage and increased apoptosis. Additionally, CQ and/or TIC combination therapy with DOX exerts its activity on the redox balance of cancer cells mediated ROS-dependent apoptosis induction achieved by GPX3 suppression. Besides, Autophagy inhibition causes moderately upregulation in ATGs 5,7 redundant proteins strengthened combinations induced apoptosis, whereas inhibition of PI3K/AKT/mTOR pathway with Beclin-1 upregulation leading to cytodestructive autophagy with overcome drug resistance effectively in curing cancer. Notably, the tumor growth inhibition and various antioxidant effects were observed in vivo. These results suggest CQ and/or TIC combination with DOX could act as effective cocktail therapy targeting autophagy and PI3K/AKT/mTOR pathways in MCF-7 breast cancer cells and hence, sensitizes cancer cells to doxorubicin treatment and combat its toxicity.

scholarly journals New Arylethanolimidazole Derivatives as HO-1 Inhibitors with Cytotoxicity against MCF-7 Breast Cancer Cells

2020 ◽  
Vol 21 (6) ◽  
pp. 1923 ◽  
Author(s):  
Valeria Ciaffaglione ◽  
Sebastiano Intagliata ◽  
Valeria Pittalà ◽  
Agostino Marrazzo ◽  
Valeria Sorrenti ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Breast Cancer Cells ◽  
Docking Studies ◽  
Hydroxyl Group ◽  
Breast Cancer Cell Lines ◽  
Heme Oxygenase 1 ◽  
Hormone Sensitive ◽  
Hydrophobic Portion ◽  
Resistant Breast Cancer Cell ◽  
Mcf 7

In this paper, a novel series of imidazole-based heme oxygenase-1 (HO-1) inhibitors is reported. These compounds were obtained by modifications of previously described high potent and selective arylethanolimidazoles. In particular, simplification of the central linker and repositioning of the hydrophobic portion were carried out. Results indicate that a hydroxyl group in the central region is crucial for the potency as well as the spatial distribution of the hydrophobic portion. Docking studies revealed a similar interaction of the classical HO-1 inhibitors with the active site of the protein. The most potent and selective compound (5a) was tested for its potential cytotoxic activity against hormone-sensitive and hormone-resistant breast cancer cell lines (MCF-7 and MDA-MB-231).

scholarly journals Inhibition of MCF-7 breast cancer cell proliferation by 5alpha-dihydrotestosterone; a role for p21(Cip1/Waf1)

2004 ◽  
Vol 32 (3) ◽  
pp. 793-810 ◽  
Author(s):  
MA Greeve ◽  
RK Allan ◽  
JM Harvey ◽  
JM Bentel
Keyword(s):  
Breast Cancer ◽  
Cell Proliferation ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
S Phase ◽  
Cyclin D3 ◽  
P27 Kip1 ◽  
Mcf 7

Androgens inhibit the growth of breast cancer cells in vitro and in vivo by mechanisms that remain poorly defined. In this study, treatment of asynchronously growing MCF-7 breast cancer cells with the androgen, 5alpha-dihydrotestosterone (DHT), was shown to inhibit cell proliferation and induce moderate increases in the proportion of G1 phase cells. Consistent with targeting the G1-S phase transition, DHT pretreatment of MCF-7 cultures impeded the serum-induced progression of G1-arrested cells into S phase and reduced the kinase activities of cyclin-dependent kinase (Cdk)4 and Cdk2 to less than 50% of controls within 3 days. DHT treatment was associated with greater than twofold increases in the levels of the Cdk inhibitor, p27(Kip1), while p21(Cip1/Waf1) protein levels remained unchanged. During the first 24 h of DHT treatment, levels of Cdk4-associated p21(Cip1/Waf1) and p27(Kip1) were reduced coinciding with decreased levels of Cdk4-associated cyclin D3. In contrast, DHT treatment caused increased accumulation of Cdk2-associated p21(Cip1/Waf1), with no significant alterations in levels of p27(Kip1) bound to Cdk2 complexes. These findings suggest that DHT reverses the Cdk4-mediated titration of p21(Cip1/Waf1) and p27(Kip1) away from Cdk2 complexes, and that the increased association of p21(Cip1/Waf1) with Cdk2 complexes in part mediates the androgen-induced growth inhibition of breast cancer cells.

scholarly journals Electrochemically Reduced Water Delays Mammary Tumors Growth in Mice and Inhibits Breast Cancer Cells SurvivalIn Vitro

2018 ◽  
Vol 2018 ◽  
pp. 1-14 ◽  
Author(s):  
Giovanni Vanni Frajese ◽  
Monica Benvenuto ◽  
Rosanna Mattera ◽  
Saverio Giampaoli ◽  
Elena Ambrosin ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Mammary Tumors ◽  
Experimental Models ◽  
Breast Cancer Cell Lines ◽  
Beneficial Effects ◽  
Significant Prolongation ◽  
Reduced Water

Electrochemical reduced water (ERW) has been proposed to have beneficial effects on human health due to its rich content of H2and the presence of platinum nanoparticles with antioxidant effects. Many studies have demonstrated that ERW scavenging properties are able to reduce the damage caused by oxidative stress in different experimental models. Although fewin vivostudies have been reported, it has been demonstrated that ERW may display anticancer effects by induction of tumor cells apoptosis and reduction of both angiogenesis and inflammation. In this study, we show that ERW treatment of MCF-7, MDA-MB-453, and mouse (TUBO) breast cancer cells inhibited cell survival in a time-dependent fashion. ERW decreased ErbB2/neuexpression and impaired pERK1/ERK2 and AKT phosphorylation in breast cancer cells. In addition, ERW treatment induced apoptosis of breast cancer cell lines independently of the status of p53 and ER and PR receptors. Ourin vivoresults showed that ERW treatment of transgenic BALB-neuT mice delayed the development of mammary tumors compared to the control. In addition, ERW induced a significant prolongation of tumor-free survival and a reduction in tumor multiplicity. Overall, these results suggest a potential beneficial role of ERW in inhibiting cancer cells growth.

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

2017 ◽  
Vol 39 (1) ◽  
pp. 25-29 ◽  
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.

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 ◽  
Mcf 7

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.

Sign in / Sign up

Export Citation Format

Share Document