scholarly journals ERβ-induced MFN2 inhibits the migration and invasiveness of breast cancer cells by inhibiting the P-AKT signaling pathway

2020 ◽  
Author(s):  
Mengyu Wei ◽  
Jun Hao ◽  
Xiaomei Liao ◽  
Yinfeng Liu ◽  
Ruihuan Fu ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Cells ◽  
Cancer Cell ◽  
Breast Cancer Cell ◽  
Breast Cancer Cells ◽  
Akt Pathway ◽  
Cancer Cell Migration ◽  
Breast Cancer Patients ◽  
Human Breast ◽  
Mcf 7

Abstract Background Mitofusin 2 (MFN2) is localized on the outer membrane of mitochondria and is closely related to the migration of malignant tumor cells. Estrogen receptor β (ERβ) plays an anticancer role in breast cancer. Our previous experiments showed that ERβ can induce MFN2 expression, which then inhibits breast cancer cell migration. However, the exact mechanism by which ERβ-induced MFN2 inhibits breast cancer cell migration is unknown. Methods In this study, immunohistochemistry was first used to detect the expression of MFN2 in breast cancer tissues, and its relationship with the clinicopathological characteristics and prognosis of breast cancer patients was analyzed. MCF-7 and MDA-MB-231 cells were transfected with ERβ and MFN2 knockdown or expression plasmids. Western blot was used to detect the effects of ERβ on MFN2 and MFN2 on P-AKT473 and MMP2; the P-AKT pathway inhibitor LY294002 was administered to cells transfected with MFN2 knockdown plasmids, Western blot, immunocytofluorescence, and a wound healing assay revealed the effect of MFN2 on its downstream signaling pathway and the migration of breast cancer cells. Results This study found that the expression of MFN2 is related to the molecular type and prognosis of breast cancer patients ( P <0.05). The positive expression rate of MFN2 in triple-negative breast cancer was significantly lower than that in the HER2 + and luminal types. However, MFN2 expression was unrelated to age, tumor size, lymph node metastasis, TNM stage, histological type and grade ( P >0.05); ERβ positively regulated MFN2 expression and reduced the migration of both MCF-7 and MDA-MB-231 cells, while MFN2 knockdown increased the expression of P-AKT473 and MMP2. In contrast, the overexpression of MFN2 inhibited the expression of P-AKT473 and MMP2. These results showed that in MFN2 knockdown cells treated with LY294002, P-AKT473 and MMP2 expression levels were reversed. The reversal of P-AKT473 and MMP2 expression levels inhibits the invasiveness of human breast cancer cells. Conclusion MFN2 is related to the molecular subtype and prognosis of breast cancer. In human breast cancer MCF-7 and MDA-MB-231 cells, ERβ-induced MFN2 can inhibit the P-AKT pathway, which inhibits the invasiveness and migration of both breast cancer cell lines.

scholarly journals Disruption of pH Dynamics Suppresses Proliferation and Potentiates Doxorubicin Cytotoxicity in Breast Cancer Cells

Pharmaceutics ◽  
2021 ◽  
Vol 13 (2) ◽  
pp. 242
Author(s):  
Diana Tavares-Valente ◽  
Bárbara Sousa ◽  
Fernando Schmitt ◽  
Fátima Baltazar ◽  
Odília Queirós
Keyword(s):  
Breast Cancer ◽  
Cancer Cells ◽  
Cell Lines ◽  
Cancer Cell ◽  
Breast Cancer Cell ◽  
Human Breast Cancer ◽  
Breast Cancer Cells ◽  
Human Breast ◽  
Cancer Tissues ◽  
Mcf 7

The reverse pH gradient is a major feature associated with cancer cell reprogrammed metabolism. This phenotype is supported by increased activity of pH regulators like ATPases, carbonic anhydrases (CAs), monocarboxylate transporters (MCTs) and sodium–proton exchangers (NHEs) that induce an acidic tumor microenvironment, responsible for the cancer acid-resistant phenotype. In this work, we analyzed the expression of these pH regulators and explored their inhibition in breast cancer cells as a strategy to enhance the sensitivity to chemotherapy. Expression of the different pH regulators was evaluated by immunofluorescence and Western blot in two breast cancer cell lines (MDA-MB-231 and MCF-7) and by immunohistochemistry in human breast cancer tissues. Cell viability, migration and invasion were evaluated upon exposure to the pH regulator inhibitors (PRIs) concanamycin-A, cariporide, acetazolamide and cyano-4-hydroxycinnamate. Additionally, PRIs were combined with doxorubicin to analyze the effect of cell pH dynamic disruption on doxorubicin sensitivity. Both cancer cell lines expressed all pH regulators, except for MCT1 and CAXII, only expressed in MCF-7 cells. There was higher plasma membrane expression of the pH regulators in human breast cancer tissues than in normal breast epithelium. Additionally, pH regulator expression was significantly associated with different molecular subtypes of breast cancer. pH regulator inhibition decreased cancer cell aggressiveness, with a higher effect in MDA-MB-231. A synergistic inhibitory effect was observed when PRIs were combined with doxorubicin in the breast cancer cell line viability. Our results support proton dynamic disruption as a breast cancer antitumor strategy and the use of PRIs to boost the activity of conventional therapy.

scholarly journals Progesterone promotes focal adhesion formation and migration in breast cancer cells through induction of protease-activated receptor-1

2012 ◽  
Vol 214 (2) ◽  
pp. 165-175 ◽  
Author(s):  
Jorge Diaz ◽  
Evelyn Aranda ◽  
Soledad Henriquez ◽  
Marisol Quezada ◽  
Estefanía Espinoza ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cell Migration ◽  
Cancer Cells ◽  
Cancer Cell ◽  
Breast Cancer Cell ◽  
Focal Adhesion ◽  
Breast Cancer Cells ◽  
Fiber Formation ◽  
Coagulation Cascade ◽  
Cancer Cell Migration

Progesterone and progestins have been demonstrated to enhance breast cancer cell migration, although the mechanisms are still not fully understood. The protease-activated receptors (PARs) are a family of membrane receptors that are activated by serine proteases in the blood coagulation cascade. PAR1 (F2R) has been reported to be involved in cancer cell migration and overexpressed in breast cancer. We herein demonstrate that PAR1 mRNA and protein are upregulated by progesterone treatment of the breast cancer cell lines ZR-75 and T47D. This regulation is dependent on the progesterone receptor (PR) but does not require PR phosphorylation at serine 294 or the PR proline-rich region mPRO. The increase in PAR1 mRNA was transient, being present at 3 h and returning to basal levels at 18 h. The addition of a PAR1-activating peptide (aPAR1) to cells treated with progesterone resulted in an increase in focal adhesion (FA) formation as measured by the cellular levels of phosphorylated FA kinase. The combined but not individual treatment of progesterone and aPAR1 also markedly increased stress fiber formation and the migratory capacity of breast cancer cells. In agreement with in vitro findings, data mining from the Oncomine platform revealed that PAR1 expression was significantly upregulated in PR-positive breast tumors. Our observation that PAR1 expression and signal transduction are modulated by progesterone provides new insight into how the progestin component in hormone therapies increases the risk of breast cancer in postmenopausal women.

Potential Mechanisms of miR-143/Krupple Like Factor 5 Axis in Impeding the Proliferation of Michigan Cancer Foundation-7 Breast Cancer Cell Line

2021 ◽  
Vol 11 (2) ◽  
pp. 326-332
Author(s):  
Le Ma ◽  
Zhenyu Liu ◽  
Zhimin Fan
Keyword(s):  
Breast Cancer ◽  
Cancer Cells ◽  
Cancer Cell ◽  
Breast Cancer Cell ◽  
Breast Cancer Cells ◽  
Cell Model ◽  
Cancer Cell Line ◽  
Breast Cancer Cell Model ◽  
Underlying Mechanisms ◽  
Mcf 7

Breast cancer is one of the most prevailing cancers in females, while the cancerous heterogeneity hinders its early diagnosis and subsequent therapy. miR-143-3p is a critical mediator in malignancy development and tumorigenesis as a tumor suppressor. Its role in various tumor entities has been investigated, such as colon cancer and breast cancer. Using MCF-7 breast cancer cell model, we planned to explore the underlying mechanisms of miR-143/KLF-5 axis in retarding breast cancer cells growth. Bioinformatics analysis searched the target KLF5 of miR-143, and the miR-143-targeted mimic and inhibitor were employed to detect the changes of KLF5. After transfection of mimic miR-143, the CCK-8 reagent assessed cell proliferation. Based on optimal stimulation time, miR-143 stimulation model was established, followed by determining expression of KLF5, EGFR and PCNA via western blot and qPCR. Eventually, siRNA-KLF5 was applied to silencing KLF5 level to evaluate its role in MCF-7 cells. The transcription and translation levels of KLF5 were diminished in miR-143-mimic transfected MCF-7 cells, while enhanced in miR-143-inhibitor transfected MCF-7 cells. When MCF-7 cells were transfected with miR-143-mimic at different time points, 48 hours was found to be the optimal transfection time, with reduced transcription and translation levels of KLF5, EGFR and PCNA. The transcription and translation levels of PNCA and EGFR were declined after silencing KLF5 by siRNA. miR-143/KLF5 axis could retard the proliferation of MCF-7 breast cancer cells.

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.

scholarly journals Interleukin-8 Promotes Epithelial-to-Mesenchymal Transition via Downregulation of Mir-200 Family in Breast Cancer Cells

2020 ◽  
Vol 19 ◽  
pp. 153303382097967
Author(s):  
Jin Zhang ◽  
Nan Shao ◽  
Xiaoyu Yang ◽  
Chuanbo Xie ◽  
Yawei Shi ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Cells ◽  
Cancer Cell ◽  
Breast Cancer Cell ◽  
Breast Cancer Cells ◽  
Epithelial To Mesenchymal Transition ◽  
Cancer Cell Line ◽  
Control Group ◽  
Mesenchymal Transition ◽  
Mcf 7

The microRNA-200 (miR-200) family has been reported to be vital for the inhibition of epithelial-to-mesenchymal transition (EMT) in tumor cells. The miR-200 family represents a complex multi-factorial regulatory network which has not been well described in breast cancer. This study aimed to clarify the underlying regulatory association between IL-8 and miR-200 family in the process of EMT in breast cancer cell. In estrogen-receptor (ER) positive breast cancer cell line MCF-7, IL-8 overexpression cells were performed by lentivirus transfection as endogenous regulation with additional exogenous IL-8 stimulation. Transient overexpressions of miR-200 family were performed after endogenous or exogenous IL-8 overexpression in MCF-7 cells. IL-8 knockdown cells were constructed via siRNA and shRNA transfection in triple negative breast cancer cell line MDA-MB-231. N-cadherin, vimentin and ZEB2 were down-regulated and E-cadherin was up-regulated in IL-8 knockdown group compared with control group. On the other hand, N-cadherin, vimentin and ZEB2 were up-regulated and E-cadherin was down-regulated in IL-8 overexpression group compared with control group. This indicated IL-8 promotes EMT in breast cancer cells. Transwell assay showed that IL-8 increased the migration and invasiveness of tumor cells. Furthermore, we performed transient overexpression of miR-200 family after endogenous or exogenous IL-8 overexpression in MCF-7 cells, which showed that the miR-200 family could inhibit EMT induced by IL-8. IL-8 promoted EMT via downregulation of miR-200 family expression in breast cancer cells and increases tumor cell migration and invasion.

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

2019 ◽  
Vol 2019 ◽  
pp. 1-13 ◽  
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.

scholarly journals Dysregulation of POPDC1 promotes breast cancer cell migration and proliferation

2017 ◽  
Vol 37 (6) ◽  
Author(s):  
Johanna Ndamwena Amunjela ◽  
Steven John Tucker
Keyword(s):  
Breast Cancer ◽  
Cell Migration ◽  
Cancer Cells ◽  
Cancer Cell ◽  
Breast Cancer Cell ◽  
Breast Cancer Cells ◽  
Cancer Cell Migration ◽  
Breast Tumorigenesis ◽  
Breast Cancer Cell Migration ◽  
Cell Migration And Proliferation

Breast cancer subtypes such as triple-negative that lack the expression of oestrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor 2 receptor (HER2), remain poorly clinically managed due to a lack of therapeutic targets. This necessitates identification and validation of novel targets. Suppression of Popeye domain-containing protein 1 (POPDC1) is known to promote tumorigenesis and correlate to poor clinical outcomes in various cancers, and also promotes cardiac and skeletal muscle pathologies. It remains to be established whether POPDC1 is dysregulated in breast cancer, and whether overcoming the dysregulation of POPDC1 could present a potential therapeutic strategy to inhibit breast tumorigenesis. We assessed the potential of POPDC1 as a novel target for inhibiting breast cancer cell migration and proliferation. POPDC1 was significantly suppressed with reduced cell membrane localization in breast cancer cells. Furthermore, functional suppression of POPDC1 promoted breast cancer cell migration and proliferation, which were inhibited by POPDC1 overexpression. Finally, cAMP interacts with POPDC1 and up-regulates its expression in breast cancer cells. These findings suggest that POPDC1 plays a role in breast tumorigenesis and represents a potential therapeutic target or biomarker in breast cancer medicine.

scholarly journals PIPERINE IN THE PREVENTION OF THE DECREASED TAMOXIFEN SENSITIVITY IN MCF-7 BREAST CANCER CELL LINE

2018 ◽  
Vol 10 (1) ◽  
pp. 335
Author(s):  
Sandy Vitria Kurniawan ◽  
Lies Sugiarti ◽  
Septelia Inawati Wanandi ◽  
Melva Louisa
Keyword(s):  
Breast Cancer ◽  
Cell Viability ◽  
Cancer Cells ◽  
Cancer Cell ◽  
Breast Cancer Cell ◽  
Breast Cancer Cells ◽  
Cancer Cell Line ◽  
P Glycoprotein ◽  
Mcf 7 ◽  
In Cells

Objective: This study was designed to analyze the role of piperine in modulating P-glycoprotein mRNA expression when added in combination withtamoxifen to breast cancer cells in culture.Methods: MCF-7 breast cancer cells were treated with 1 μM tamoxifen with or without piperine (12.5, 25, or 50 μM) or verapamil 50 μM (P-glycoproteininhibitor positive control) for up to 12 days. We assessed the cell viability and isolated total RNA from them. We quantified P-glycoprotein expressionsusing quantitative reverse transcription polymerase chain reaction.Results: Administration of various doses of piperine decreased MCF-7 breast cancer cell viability. Piperine, when given in combination with tamoxifen,decreased the expression of P-glycoprotein mRNA in cells compared with the expression in cells treated with tamoxifen only. The effects were shownto be dose dependent.Conclusion: Piperine prevents the development of breast cancer cell tamoxifen resistance, probably through its inhibition of P-glycoprotein expression.

Determination of Vulpinic Acid Effect on Apoptosis and mRNA Expression Levels in Breast Cancer Cell Lines

2019 ◽  
Vol 18 (14) ◽  
pp. 2032-2041 ◽  
Author(s):  
Nil Kılıç ◽  
Sümer Aras ◽  
Demet Cansaran-Duman
Keyword(s):  
Breast Cancer ◽  
Cell Viability ◽  
Cancer Cells ◽  
Cell Line ◽  
Cell Lines ◽  
Cancer Cell ◽  
Breast Cancer Cell ◽  
Breast Cancer Cells ◽  
Breast Cancer Cell Lines ◽  
Human Breast

Objective: Breast cancer is one of the most common diseases among women worldwide and it is characterized by a high ratio of malignancy and metastasis and low rate of survival of patients. Due to limited treatment options, the discovery of alternative therapeutic agents and clarifying the molecular mechanism of breast cancer development may offer new hope for its treatment. Lichen secondary metabolites may be one of these therapeutic agents. Methods: In this study, the effects of Vulpinic Acid (VA) lichen secondary metabolite on the cell viability and apoptosis of breast cancer cells and non-cancerous cell line were investigated. Quantitative polymerase chain reaction was also performed to determine changes in the expression of apoptosis-related genes at a molecular level. Results: The results demonstrated that VA significantly inhibited the cell viability and induced apoptosis of human breast cancer cells. The highest rates of decreased growth were determined using the IC50 value of VA for 48h on MCF-7 breast cancer cell. Interestingly, VA treatment significantly reduced cell viability in all examined breast cancer cell lines compared to their non-cancerous human breast epithelial cell line. This is the first study on the investigation of the effects of VA on the molecular mechanisms associated with the expression of apoptosis-related genes in breast cancer cell lines. Results demonstrated that the gene expression of P53 genes was altered up to fourteen-fold levels in SK-BR-3 cell lines whereas it reached 2.5-fold in the MCF-12A cell line after treatment with VA. These observations support that VA induces apoptosis on the breast cancer cells compared with the non-cancerous human breast epithelial cell line. Conclusion: It is implicated that VA may be a promising novel molecule for the induction of apoptosis on breast cancer cells.

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