scholarly journals Overexpression of β-Arrestins inhibits proliferation and motility in triple negative breast cancer cells

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Saber Yari Bostanabad ◽  
Senem Noyan ◽  
Bala Gur Dedeoglu ◽  
Hakan Gurdal
Keyword(s):  
Breast Cancer ◽  
Cell Cycle ◽  
Cancer Cells ◽  
Cancer Cell ◽  
Breast Cancer Cells ◽  
Cell Function ◽  
Expression Profiles ◽  
Tissue Samples ◽  
Expression Levels ◽  
Cell Cycle Genes

Abstractβ-Arrestins (βArrs) are intracellular signal regulating proteins. Their expression level varies in some cancers and they have a significant impact on cancer cell function. In general, the significance of βArrs in cancer research comes from studies examining GPCR signalling. Given the diversity of different GPCR signals in cancer cell regulation, contradictory results are inevitable regarding the role of βArrs. Our approach examines the direct influence of βArrs on cellular function and gene expression profiles by changing their expression levels in breast cancer cells, MDA-MB-231 and MDA-MB-468. Reducing expression of βArr1 or βArr2 tended to increase cell proliferation and invasion whereas increasing their expression levels inhibited them. The overexpression of βArrs caused cell cycle S-phase arrest and differential expression of cell cycle genes, CDC45, BUB1, CCNB1, CCNB2, CDKN2C and reduced HER3, IGF-1R, and Snail. Regarding to the clinical relevance of our results, low expression levels of βArr1 were inversely correlated with CDC45, BUB1, CCNB1, and CCNB2 genes compared to normal tissue samples while positively correlated with poorer prognosis in breast tumours. These results indicate that βArr1 and βArr2 are significantly involved in cell cycle and anticancer signalling pathways through their influence on cell cycle genes and HER3, IGF-1R, and Snail in TNBC cells.

scholarly journals The Role of Transient Receptor Potential Melastatin 7 (TRPM7) in Cell Viability: A Potential Target to Suppress Breast Cancer Cell Cycle

Cancers ◽  
2020 ◽  
Vol 12 (1) ◽  
pp. 131 ◽  
Author(s):  
Hengrui Liu ◽  
James P. Dilger ◽  
Jun Lin
Keyword(s):  
Breast Cancer ◽  
Cell Cycle ◽  
Cancer Cells ◽  
Cancer Cell ◽  
Divalent Cation ◽  
Breast Cancer Cells ◽  
Transient Receptor Potential ◽  
Receptor Potential ◽  
Transient Receptor Potential Melastatin ◽  
Transient Receptor

The divalent cation-selective channel transient receptor potential melastatin 7 (TRPM7) channel was shown to affect the proliferation of some types of cancer cell. However, the function of TRPM7 in the viability of breast cancer cells remains unclear. Here we show that TRPM inhibitors suppressed the viability of TRPM7-expressing breast cancer cells. We first demonstrated that the TRPM7 inhibitors 2-aminoethyl diphenylborinate (2-APB), ginsenoside Rd (Gin Rd), and waixenicin A preferentially suppressed the viability of human embryonic kidney HEK293 overexpressing TRPM7 (HEK-M7) cells over wildtype HEK293 (WT-HEK). Next, we confirmed the effects of 2-APB on the TRPM7 channel functions by whole-cell currents and divalent cation influx. The inhibition of the viability of HEK-M7 cells by 2-APB was not mediated by the increase in cell death but by the interruption of the cell cycle. Similar to HEK-M7 cells, the viability of TRPM7-expressing human breast cancer MDA-MB-231, AU565, and T47D cells were also suppressed by 2-APB by arresting the cell cycle in the S phase. Furthermore, in a novel TRPM7 knock-out MDA-MB-231 (KO-231) cell line, decreased divalent influx and reduced proliferation were observed compared to the wildtype MDA-MB-231 cells. 2-APB and Gin Rd preferentially suppressed the viability of wildtype MDA-MB-231 cells over KO-231 by affecting the cell cycle in wildtype but not KO-231 cells. Our results suggest that TRPM7 regulates the cell cycle of breast cancers and is a potential therapeutic target.

scholarly journals αO-Conotoxin GeXIVA Inhibits the Growth of Breast Cancer Cells via Interaction with α9 Nicotine Acetylcholine Receptors

Marine Drugs ◽  
2020 ◽  
Vol 18 (4) ◽  
pp. 195 ◽  
Author(s):  
Zhihua Sun ◽  
Jiaolin Bao ◽  
Manqi Zhangsun ◽  
Shuai Dong ◽  
Dongting Zhangsun ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cell Cycle ◽  
Flow Cytometry ◽  
Cell Cycle Arrest ◽  
Cancer Cells ◽  
Cell Line ◽  
Cancer Cell ◽  
Breast Cancer Cell ◽  
Breast Cancer Cells ◽  
Cycle Arrest

The α9-containing nicotinic acetylcholine receptor (nAChR) is increasingly emerging as a new tumor target owing to its high expression specificity in breast cancer. αO-Conotoxin GeXIVA is a potent antagonist of α9α10 nAChR. Nevertheless, the anti-tumor effect of GeXIVA on breast cancer cells remains unclear. Cell Counting Kit-8 assay was used to study the cell viability of breast cancer MDA-MD-157 cells and human normal breast epithelial cells, which were exposed to different doses of GeXIVA. Flow cytometry was adopted to detect the cell cycle arrest and apoptosis of GeXIVA in breast cancer cells. Migration ability was analyzed by wound healing assay. Western blot (WB), quantitative real-time PCR (QRT-PCR) and flow cytometry were used to determine expression of α9-nAChR. Stable MDA-MB-157 breast cancer cell line, with the α9-nAChR subunit knocked out (KO), was established using the CRISPR/Cas9 technique. GeXIVA was able to significantly inhibit the proliferation and promote apoptosis of breast cancer MDA-MB-157 cells. Furthermore, the proliferation of breast cancer MDA-MB-157 cells was inhibited by GeXIVA, which caused cell cycle arrest through downregulating α9-nAChR. GeXIVA could suppress MDA-MB-157 cell migration as well. This demonstrates that GeXIVA induced a downregulation of α9-nAChR expression, and the growth of MDA-MB-157 α9-nAChR KO cell line was inhibited as well, due to α9-nAChR deletion. GeXIVA inhibits the growth of breast cancer cell MDA-MB-157 cells in vitro and may occur in a mechanism abolishing α9-nAChR.

scholarly journals PSIP1/p75 promotes tumorigenicity in breast cancer cells by promoting the transcription of cell cycle genes

2017 ◽  
Vol 38 (10) ◽  
pp. 966-975 ◽  
Author(s):  
Deepak K Singh ◽  
Omid Gholamalamdari ◽  
Mahdieh Jadaliha ◽  
Xiao Ling Li ◽  
Yo-Chuen Lin ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cell Cycle ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Cell Cycle Genes

scholarly journals α-Mangostin Induces Apoptosis and Inhibits Metastasis of Breast Cancer Cells via Regulating RXRα-AKT Signaling Pathway

2021 ◽  
Vol 12 ◽  
Author(s):  
Xiuzhi Zhu ◽  
Jialin Li ◽  
Huiting Ning ◽  
Zhidong Yuan ◽  
Yue Zhong ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cell Cycle ◽  
Cyclin D1 ◽  
Cancer Cells ◽  
Signaling Pathway ◽  
Cancer Cell ◽  
Breast Cancer Cell ◽  
Breast Cancer Cells ◽  
Akt Signaling ◽  
Akt Signaling Pathway

Mangostin, which has the function of anti-inflammatory, antioxidant, and anticancer, etc, is one of the main active ingredients of the hull of the mangosteen. The main objective of the study was to elucidate its anti-cancer function and possible mechanism. α-Mangostin was separated and structurally confirmed. MTT method was used to check the effect of mangostin on breast cancer cell proliferation. Then the effect of α-Mangostin on the transcriptional activity of RXRα was tested by dual-luciferase reporter gene assay. And Western blot (WB) was used to detect the expression of apoptosis-related proteins or cell cycle-associated proteins after treatment. Also, this study was to observe the effects of α-Mangostin on the invasion of breast cancer cell line MDA-MB-231. α-Mangostin regulates the downstream effectors of the PI3K/AKT signaling pathway by degrading RXRα/tRXRα. α-Mangostin can trigger PARP cleavage and induce apoptosis, which may be related to the induction of upregulated BAX expression and downregulation of BAD and cleaved caspase-3 expression in MDA-MB-231 cells through blockade of AKT signaling. The experiments verify that α-Mangostin have evident inhibition effects of invasion and metastasis of MDA-MB-231 cells. Cyclin D1 was involved in the anticancer effects of α-Mangostin on the cell cycle in MDA-MB-231 cells. α-Mangostin induces apoptosis, suppresses the migration and invasion of breast cancer cells through the PI3K/AKT signaling pathway by targeting RXRα, and cyclin D1 has involved in this process.

Activin and estrogen crosstalk regulates transcription in human breast cancer cells

2007 ◽  
Vol 14 (3) ◽  
pp. 679-689 ◽  
Author(s):  
Joanna E Burdette ◽  
Teresa K Woodruff
Keyword(s):  
Breast Cancer ◽  
Cell Cycle ◽  
Cell Cycle Arrest ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Transforming Growth Factor ◽  
Cell Function ◽  
Cycle Arrest ◽  
Mammary Cell ◽  
Pai 1

Activin is a member of the transforming growth factor β superfamily that regulates mammary cell function during development, lactation, and in cancer. Activin slows the growth of breast cancer cells by inducing G0/G1 cell cycle arrest. Estrogen is a steroid hormone that stimulates the proliferation of mammary epithelial cells in development and oncogenesis. The crosstalk between estrogen and activin that regulates activin ligand expression, activin and estrogen signal transduction, and cell cycle arrest was investigated in this study. Estrogen antagonized activin-dependent production of plasminogen activator inhibitor 1 (PAI-1) mRNA, while activin repressed estrogen-dependent transcription of trefoil factor 1. The repression of estrogen signaling by activin was recapitulated using a simple estrogen response element-luciferase construct and was enhanced in the presence of overexpressed estrogen receptor α (ERα). In contrast, estrogen-mediated repression of activin signaling could not be recapitulated on a simple CAGA Smad-binding element but did inhibit the short PAI-1 promoter, p3TP-luciferase, especially when ERα was overexpressed. Repression of both estrogen- and activin-regulated transcription was found to be ligand induced and Smad3 dependent. In addition to transcriptional repression, estrogen also reduced the amount of activin B mRNA and protein produced by MCF7 breast cancer cells. These studies demonstrate the importance of activin and estrogen crosstalk during mammary cell growth and cancer initiation.

scholarly journals Antibody–drug nanoparticle induces synergistic treatment efficacies in HER2 positive breast cancer cells

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Muhammad Raisul Abedin ◽  
Kaitlyne Powers ◽  
Rachel Aiardo ◽  
Dibbya Barua ◽  
Sutapa Barua
Keyword(s):  
Breast Cancer ◽  
Cell Cycle ◽  
Cancer Cells ◽  
Cancer Cell ◽  
Breast Cancer Cells ◽  
Her2 Positive ◽  
Her2 Positive Breast Cancer ◽  
Anti Cancer ◽  
Antibody Drug ◽  
Positive Breast Cancer

AbstractChemotherapeutic drugs suffer from non-specific binding, undesired toxicity, and poor blood circulation which contribute to poor therapeutic efficacy. In this study, antibody–drug nanoparticles (ADNs) are engineered by synthesizing pure anti-cancer drug nanorods (NRs) in the core of nanoparticles with a therapeutic monoclonal antibody, Trastuzumab on the surface of NRs for specific targeting and synergistic treatments of human epidermal growth factor receptor 2 (HER2) positive breast cancer cells. ADNs were designed by first synthesizing ~ 95 nm diameter × ~ 500 nm long paclitaxel (PTX) NRs using the nanoprecipitation method. The surface of PTXNRs was functionalized at 2′ OH nucleophilic site using carbonyldiimidazole and conjugated to TTZ through the lysine residue interaction forming PTXNR-TTZ conjugates (ADNs). The size, shape, and surface charge of ADNs were characterized using scanning electron microscopy (SEM), SEM, and zeta potential, respectively. Using fluorophore labeling and response surface analysis, the percentage conjugation efficiency was found > 95% with a PTX to TTZ mass ratio of 4 (molar ratio ≈ 682). In vitro therapeutic efficiency of PTXNR-TTZ was evaluated in two HER2 positive breast cancer cell lines: BT-474 and SK-BR-3, and a HER2 negative MDA-MB-231 breast cancer cell using MTT assay. PTXNR-TTZ inhibited > 80% of BT-474 and SK-BR-3 cells at a higher efficiency than individual PTX and TTZ treatments alone after 72 h. A combination index analysis indicated a synergistic combination of PTXNR-TTZ compared with the doses of single-drug treatment. Relatively lower cytotoxicity was observed in MCF-10A human breast epithelial cell control. The molecular mechanisms of PTXNR-TTZ were investigated using cell cycle and Western blot analyses. The cell cycle analysis showed PTXNR-TTZ arrested > 80% of BT-474 breast cancer cells in the G2/M phase, while > 70% of untreated cells were found in the G0/G1 phase indicating that G2/M arrest induced apoptosis. A similar percentage of G2/M arrested cells was found to induce caspase-dependent apoptosis in PTXNR-TTZ treated BT-474 cells as revealed using Western blot analysis. PTXNR-TTZ treated BT-474 cells showed ~ 1.3, 1.4, and 1.6-fold higher expressions of cleaved caspase-9, cytochrome C, and cleaved caspase-3, respectively than untreated cells, indicating up-regulation of caspase-dependent activation of apoptotic pathways. The PTXNR-TTZ ADN represents a novel nanoparticle design that holds promise for targeted and efficient anti-cancer therapy by selective targeting and cancer cell death via apoptosis and mitotic cell cycle arrest.

scholarly journals Orai2 Modulates Store-Operated Ca2+ Entry and Cell Cycle Progression in Breast Cancer Cells

Cancers ◽  
2021 ◽  
Vol 14 (1) ◽  
pp. 114
Author(s):  
Jose Sanchez-Collado ◽  
Jose J. Lopez ◽  
Carlos Cantonero ◽  
Isaac Jardin ◽  
Sergio Regodón ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cell Cycle ◽  
Cancer Cells ◽  
Cell Lines ◽  
Cancer Cell ◽  
Breast Cancer Cell ◽  
Breast Cancer Cells ◽  
Cancer Cell Lines ◽  
Breast Cancer Cell Lines ◽  
Apoptosis Resistance

Breast cancer is a heterogeneous disease from the histological and molecular expression point of view, and this heterogeneity determines cancer aggressiveness. Store-operated Ca2+ entry (SOCE), a major mechanism for Ca2+ entry in non-excitable cells, is significantly remodeled in cancer cells and plays an important role in the development and support of different cancer hallmarks. The store-operated CRAC (Ca2+ release-activated Ca2+) channels are predominantly comprised of Orai1 but the participation of Orai2 and Orai3 subunits has been reported to modulate the magnitude of Ca2+ responses. Here we provide evidence for a heterogeneous expression of Orai2 among different breast cancer cell lines. In the HER2 and triple negative breast cancer cell lines SKBR3 and BT20, respectively, where the expression of Orai2 was greater, Orai2 modulates the magnitude of SOCE and sustain Ca2+ oscillations in response to carbachol. Interestingly, in these cells Orai2 modulates the activation of NFAT1 and NFAT4 in response to high and low agonist concentrations. Finally, we have found that, in cells with high Orai2 expression, Orai2 knockdown leads to cell cycle arrest at the G0-G1 phase and decreases apoptosis resistance upon cisplatin treatment. Altogether, these findings indicate that, in breast cancer cells with a high Orai2 expression, Orai2 plays a relevant functional role in agonist-evoked Ca2+ signals, cell proliferation and apoptosis resistance.

scholarly journals Treatment with DHA Modifies the Response of MDA-MB-231 Breast Cancer Cells and Tumors from nu/nu Mice to Doxorubicin through Apoptosis and Cell Cycle Arrest

2019 ◽  
Vol 149 (1) ◽  
pp. 46-56 ◽  
Author(s):  
Marnie Newell ◽  
Miranda Brun ◽  
Catherine J Field
Keyword(s):  
Breast Cancer ◽  
Cell Cycle ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Cyclin B1 ◽  
Cell Cycle Genes ◽  
Cycle Arrest ◽  
And Function

ABSTRACT Background Docosahexaenoic acid (DHA) has been shown to reduce growth of breast cancer cells in vitro and in vivo; it may also benefit the action of cytotoxic cancer drugs. The mechanisms for these observations are not completely understood. Objectives We sought to explore how pretreatment of MDA-MB-231 breast cancer cells with DHA alters gene expression with doxorubicin (DOX) treatment and confirm that feeding DHA to tumor-bearing nu/nu mice improves the efficacy of DOX. Methods MDA-MB-231 cells were subjected to 4 conditions: a control mixture of 40 μM linoleic and 40 μM oleic acid (OALA), DHA (60 μM plus OALA), OALA DOX (0.41 μM), or DHA DOX (plus OALA) and assessed for effects on viability and function. Female nu/nu mice (6 wk old) bearing MDA-MB-231 tumors were randomly assigned to a nutritionally complete diet (20 g ± 2.8 g DHA/100 g diet) containing a polyunsaturated:saturated fat ratio of 0.5, with or without injections 2 times/wk of 5 mg DOX/kg for 4 wk. Results Microarray and protein analysis indicated that DHA DOX cells, compared with OALA DOX, had upregulated expression of apoptosis genes, Caspase-10 (1.3-fold), Caspase-9 (1.4-fold), and Receptor (TNFRSF)-interacting serine-threonine kinase 1 (RIPK1) (1.2-fold), while downregulating cell cycle genes, Cyclin B1 (−2.1-fold), WEE1 (−1.6-fold), and cell division cycle 25 homolog C (CDC25C) (−1.8-fold) (P < 0.05). DHA DOX–treated mice had 50% smaller tumors than control mice (P < 0.05). Analysis of proapoptotic proteins from tumors of DHA DOX mice showed increased Caspase-10 (by 68%) and BH3 interacting domain death agonist (Bid) (by 50%), decreased B-cell CLL/lymphoma 2 (BCL2) (by 24%), and decreased cell cycle proteins Cyclin B1 and Cdc25c (both by 42%), compared with control mice (P < 0.05). Conclusions Supplementation with DHA facilitates the action of DOX in MDA-MB-231 cells and in nu/nu mice, which may occur via amplification of the effect of DOX on apoptosis and cell cycle genes.

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