Acrylamide-encapsulated glucose oxidase inhibits breast cancer cell viability

2020 ◽  
Vol 0 (0) ◽  
Author(s):  
Trëndelina Rrustemi ◽  
Öykü Gönül Geyik ◽  
Ali Burak Özkaya ◽  
Taylan Kurtuluş Öztürk ◽  
Zeynep Yüce ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Glucose Oxidase ◽  
Cancer Cells ◽  
Half Life ◽  
Neutralizing Antibodies ◽  
Redox Homeostasis ◽  
Proteinase K ◽  
Dependent Manner ◽  
Production Of Hydrogen ◽  
Mcf 7

AbstractObjectivesCancer cells modulate metabolic pathways to ensure continuity of energy, macromolecules and redox- homeostasis. Although these vulnerabilities are often targeted individually, targeting all with an enzyme may prove a novel approach. However, therapeutic enzymes are prone to proteolytic degradation and neutralizing antibodies leading to a reduced half-life and effectiveness. We hypothesized that glucose oxidase (GOX) enzyme that catalyzes oxidation of glucose and production of hydrogen peroxide, may hit all these targets by depleting glucose; crippling anabolic pathways and producing reactive oxygen species (ROS); unbalancing redox homeostasis.MethodsWe encapsulated GOX in an acrylamide layer and then performed activity assays in denaturizing settings to determine protection provided by encapsulation. Afterwards, we tested the effects of encapsulated (enGOX) and free (fGOX) enzyme on MCF-7 breast cancer cells.ResultsGOX preserved 70% of its activity following encapsulation. When fGOX and enGOX treated with guanidinium chloride, fGOX lost approximately 72% of its activity, while enGOX only lost 30%. Both forms demonstrated remarkable resilience against degradation by proteinase K and inhibited viability of MCF-7 cells in an activity-dependent manner.ConclusionsEncapsulation provided protection to GOX against denaturation without reducing its activity, which would prolong half-life of the enzyme when administered intravenously.

scholarly journals HER2 (neu) Signaling Increases the Rate of Hypoxia-Inducible Factor 1α (HIF-1α) Synthesis: Novel Mechanism for HIF-1-Mediated Vascular Endothelial Growth Factor Expression

2001 ◽  
Vol 21 (12) ◽  
pp. 3995-4004 ◽  
Author(s):  
Erik Laughner ◽  
Panthea Taghavi ◽  
Kelly Chiles ◽  
Patrick C. Mahon ◽  
Gregg L. Semenza
Keyword(s):  
Breast Cancer ◽  
Vascular Endothelial Growth Factor ◽  
Growth Factor ◽  
Cancer Cells ◽  
Half Life ◽  
Hypoxia Inducible Factor ◽  
Dependent Manner ◽  
Vascular Endothelial ◽  
Her2 Signaling ◽  
Endothelial Growth Factor

ABSTRACT Hypoxia-inducible factor 1 (HIF-1) is a transcriptional activator composed of HIF-1α and HIF-1β subunits. Several dozen HIF-1 targets are known, including the gene encoding vascular endothelial growth factor (VEGF). Under hypoxic conditions, HIF-1α expression increases as a result of decreased ubiquitination and degradation. The tumor suppressors VHL (von Hippel-Lindau protein) and p53 target HIF-1α for ubiquitination such that their inactivation in tumor cells increases the half-life of HIF-1α. Increased phosphatidylinositol 3-kinase (PI3K) and AKT or decreased PTEN activity in prostate cancer cells also increases HIF-1α expression by an undefined mechanism. In breast cancer, increased activity of the HER2 (also known as neu) receptor tyrosine kinase is associated with increased tumor grade, chemotherapy resistance, and decreased patient survival. HER2 has also been implicated as an inducer of VEGF expression. Here we demonstrate that HER2 signaling induced by overexpression in mouse 3T3 cells or heregulin stimulation of human MCF-7 breast cancer cells results in increased HIF-1α protein and VEGF mRNA expression that is dependent upon activity of PI3K, AKT (also known as protein kinase B), and the downstream kinase FRAP (FKBP-rapamycin-associated protein). In contrast to other inducers of HIF-1 expression, heregulin stimulation does not affect the half-life of HIF-1α but instead stimulates HIF-1α synthesis in a rapamycin-dependent manner. The 5′-untranslated region of HIF-1α mRNA directs heregulin-inducible expression of a heterologous protein. These data provide a molecular basis for VEGF induction and tumor angiogenesis by heregulin-HER2 signaling and establish a novel mechanism for the regulation of HIF-1α expression.

scholarly journals Comparison of the effect of rhodium citrate-associated iron oxide nanoparticles on metastatic and non-metastatic breast cancer cells

2019 ◽  
Vol 10 (1) ◽  
Author(s):  
Natalia Lemos Chaves ◽  
Danilo Aquino Amorim ◽  
Cláudio Afonso Pinho Lopes ◽  
Irina Estrela-Lopis ◽  
Julia Böttner ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Cells ◽  
Cell Lines ◽  
Breast Cancer Cells ◽  
Human Tumor ◽  
Metastatic Breast ◽  
Cytotoxic Action ◽  
Dependent Manner ◽  
Metastatic Cells ◽  
Mcf 7

Abstract Background Nanocarriers have the potential to improve the therapeutic index of currently available drugs by increasing drug efficacy, lowering drug toxicity and achieving steady-state therapeutic levels of drugs over an extended period. The association of maghemite nanoparticles (NPs) with rhodium citrate (forming the complex hereafter referred to as MRC) has the potential to increase the specificity of the cytotoxic action of the latter compound, since this nanocomposite can be guided or transported to a target by the use of an external magnetic field. However, the behavior of these nanoparticles for an extended time of exposure to breast cancer cells has not yet been explored, and nor has MRC cytotoxicity comparison in different cell lines been performed until now. In this work, the effects of MRC NPs on these cells were analyzed for up to 72 h of exposure, and we focused on comparing NPs’ therapeutic effectiveness in different cell lines to elect the most responsive model, while elucidating the underlying action mechanism. Results MRC complexes exhibited broad cytotoxicity on human tumor cells, mainly in the first 24 h. However, while MRC induced cytotoxicity in MDA-MB-231 in a time-dependent manner, progressively decreasing the required dose for significant reduction in cell viability at 48 and 72 h, MCF-7 appears to recover its viability after 48 h of exposure. The recovery of MCF-7 is possibly explained by a resistance mechanism mediated by PGP (P-glycoprotein) proteins, which increase in these cells after MRC treatment. Remaining viable tumor metastatic cells had the migration capacity reduced after treatment with MRC (24 h). Moreover, MRC treatment induced S phase arrest of the cell cycle. Conclusion MRC act at the nucleus, inhibiting DNA synthesis and proliferation and inducing cell death. These effects were verified in both tumor lines, but MDA-MB-231 cells seem to be more responsive to the effects of NPs. In addition, NPs may also disrupt the metastatic activity of remaining cells, by reducing their migratory capacity. Our results suggest that MRC nanoparticles are a promising nanomaterial that can provide a convenient route for tumor targeting and treatment, mainly in metastatic cells.

scholarly journals SGK3 Is an Estrogen-Inducible Kinase Promoting Estrogen-Mediated Survival of Breast Cancer Cells

2011 ◽  
Vol 25 (1) ◽  
pp. 72-82 ◽  
Author(s):  
Yuanzhong Wang ◽  
Dujin Zhou ◽  
Sheryl Phung ◽  
Selma Masri ◽  
David Smith ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Protein Kinase ◽  
Cell Survival ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Dependent Manner ◽  
Binding Regions ◽  
Er Positive ◽  
Mcf 7 ◽  
Positive Breast Cancer

Serum- and glucocorticoid-inducible kinase 3 (SGK3) is a protein kinase of the AGC family of protein kinase A, protein kinase G, and protein kinase C and functions downstream of phosphatidylinositol 3-kinase (PI3K). Recent study revealed that SGK3 plays a pivotal role in Akt/protein kinase B independent signaling downstream of oncogenic PI3KCA mutations in breast cancer. Here we report that SGK3 is an estrogen receptor (ER) transcriptional target and promotes estrogen-mediated cell survival of ER-positive breast cancer cells. Through a meta-analysis on 22 microarray studies of breast cancer in the Oncomine database, we found that the expression of SGK3 is significantly higher (5.7-fold, P < 0.001) in ER-positive tumors than in ER-negative tumors. In ER-positive breast cancer cells, SGK3 expression was found to be induced by 17β-estradiol (E2) in a dose- and time-dependent manner, and the induction of SGK3 mRNA by E2 is independent of newly synthesized proteins. We identified two ERα-binding regions at the sgk3 locus through chromatin immunoprecipitation with massively parallel DNA sequencing. Promoter analysis revealed that ERα stimulates the activity of sgk3 promoters by interaction with these two ERα-binding regions on E2 treatment. Loss-of-function analysis indicated that SGK3 is required for E2-mediated cell survival of MCF-7 breast carcinoma cells. Moreover, overexpression of SGK3 could partially protect MCF-7 cells against apoptosis caused by antiestrogen ICI 182,780. Together, our study defines the molecular mechanism of regulation of SGK3 by estrogen/ER and provides a new link between the PI3K pathway and ER signaling as well as a new estrogen-mediated cell survival mechanism mediated by SGK3 in breast cancer cells.

scholarly journals VP-128, a novel oestradiol-platinum(II) hybrid with selective anti-tumour activity towards hormone-dependent breast cancer cells in vivo

2009 ◽  
Vol 16 (4) ◽  
pp. 1185-1195 ◽  
Author(s):  
Céline Van Themsche ◽  
Sophie Parent ◽  
Valérie Leblanc ◽  
Caroline Descôteaux ◽  
Anne-Marie Simard ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Nuclear Accumulation ◽  
Dependent Manner ◽  
Anti Tumour Activity ◽  
Tumour Activity ◽  
Mcf 7

We have previously reported the synthesis of VP-128, a new 17β-oestradiol (E2)-linked platinum(II) hybrid with high affinity for oestrogen receptor α (ERα). In the present study, we have investigated the anti-tumour activity of VP-128 towards breast cancer cells in vitro and in vivo. We used human ERα-positive (MCF-7) and -negative (MDA-MB-468) cells as a model for treatment with increasing doses of VP-128, cisplatin or E2 in vitro and for xenograft experiments in nude mice in vivo. Compared with cisplatin, VP-128 showed markedly improved in vitro and in vivo anti-tumour activity towards ERα-positive MCF-7 breast cancer cells, without increased systemic toxicity. In these caspase-3-deficient cells, treatment with VP-128 overcame weak cellular sensitivity to cisplatin in vitro and in vivo. In these cells, only the hybrid induced apoptosis in an ERα-dependent manner, inactivated both X-linked inhibitor of apoptosis protein and Akt, and induced selective nuclear accumulation of ERα and the expression of ER-regulated genes c-myc and tff1, which was blocked by ERα-specific antagonist ICI 282 780. In the case of ERα-negative MDA-MB-468 cells, VP-128, but not cisplatin, induced nuclear accumulation of apoptosis-inducing factor and inhibited c-myc expression. However, VP-128 did not show enhanced in vivo anti-tumour activity compared with cisplatin. These results reveal two different modes of action for VP-128 in ERα-positive and -negative breast cancer cells, and highlight the promising therapeutic value of this unique E2-platinum hybrid for selective targeting of hormone-dependent cancers.

Estrogenic and antiestrogenic regulation of the half-life of covalently labeled estrogen receptor in MCF-7 breast cancer cells

1996 ◽  
Vol 57 (3-4) ◽  
pp. 203-213 ◽  
Author(s):  
Manuel Borrás ◽  
Ioanna Laios ◽  
Abdelhamid El Khissiin ◽  
Hye-Sook Seo ◽  
France Lempereur ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Estrogen Receptor ◽  
Cancer Cells ◽  
Half Life ◽  
Breast Cancer Cells ◽  
Mcf 7

scholarly journals Global transcriptome analysis reveals partial estrogen-like effects of karanjin in MCF-7 breast cancer cells

2021 ◽  
Author(s):  
Gaurav Bhatt ◽  
Akshita Gupta ◽  
Latha Rangan ◽  
Anil Mukund Limaye
Keyword(s):  
Breast Cancer ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Target Genes ◽  
Biological Activities ◽  
Biological Effects ◽  
Dependent Manner ◽  
Cell Type ◽  
Concentration Dependent Manner ◽  
Mcf 7

Karanjin, an abundantly occurring furanoflavonoid in edible and non-edible legumes, exerts diverse biological effects in vivo, and in vitro. Its potential as an anticancer agent is also gaining traction following recent demonstrations of its anti-proliferative, cell cycle inhibitory, and pro-apoptotic effects. However, the universality of its anticancer potential is yet to be scrutinized, particularly so because flavonoids can act as selective estrogen receptor modulators (SERMs). Even the genomic correlates of its biological activities are yet to be examined in hormone responsive cells. This paper presents the early and direct transcriptomic footprint of 10 μM karanjin in MCF-7 breast cancer cells, using next generation sequencing technology (RNA-seq). We show that karanjin-modulated gene-expression repertoire is enriched in several hallmark gene sets, which include early estrogen-response, and G2/M checkpoint genes. Genes modulated by karanjin overlapped with those modulated by 1 nM 17β-estradiol (E2), or 1 μM tamoxifen. Karanjin altered the expression of selected estrogen-regulated genes in a cell-type, and concentration dependent manner. It downmodulated the expression of ERα protein in MCF-7 cells. Furthermore, ERα knockdown negatively impacted karanjins ability to modulate the expression of selected E2 target genes. Our data suggest that karanjin exerts its effects on ERα-positive breast cancer cells, at least in part, via ERα. The apparent SERM-like effects of karanjin pose a caveat to the anticancer potential of karanjin. In-depth studies on cell-type and concentration-dependent effects of karanjin may bring out its true potential in endocrine therapies.

scholarly journals Exploring the Mechanism of Baicalin Intervention in Breast Cancer Based on MicroRNA Microarrays and Bioinformatics Strategies

2021 ◽  
Vol 2021 ◽  
pp. 1-10
Author(s):  
Anqi Ge ◽  
Lifang Liu ◽  
Xian’guang Deng ◽  
Jun Luo ◽  
Yanghua Xu
Keyword(s):  
Breast Cancer ◽  
Cancer Cells ◽  
Signaling Pathway ◽  
Breast Cancer Cells ◽  
Enrichment Analysis ◽  
Dependent Manner ◽  
P53 Signaling ◽  
Microrna Microarrays ◽  
P53 Signaling Pathway ◽  
Mcf 7

Objective. To explore the mechanism of baicalin intervention in breast cancer based on microRNA microarrays. Methods. The inhibitory rate of baicalin intervention in MCF-7 breast cancer cells was determined by MTT. Then, the miRNA microarrays were used to validate the key microRNAs. After that, reverse transcription-quantitative polymerase chain reaction (RT-qPCR) was used to validate microRNA, hsa-miR-15a, hsa-miR-100, hsa-miR-16, and hsa-miR-7t. Finally, the potential targets of these key microRNAs are predicted by miRWalk, and DAVID was utilized for gene ontology (GO) enrichment analysis and pathway enrichment analysis. Results. Baicalin may inhibit the proliferation of MCF-7 cells in a dose-dependent and time-dependent manner. The concentration of baicalin 150 μmol/L was determined for the subsequent miRNA chip research. A total of 92 upregulated microRNAs and 35 downregulated microRNAs were obtained. The upregulated miRNAs include hsa-miR-6799-5p, hsa-miR-6126, hsa-miR-4792, hsa-miR-6848-5p, hsa-miR-3197, hsa-miR-6779-5p, and hsa-miR -654-5p. The downregulated miRNAs include hsa-miR-3911, hsa-miR-504-5p, hsa-miR-30a-3p, hsa-miR-193b-3p, and hsa-miR-181b-5p. Then, differentially expressed miRNA was verified by qRT-PCR. The results showed that the expression of hsa-miR-15a, hsa-miR-100, hsa-miR-16, and hsa-let-7c was upregulated ( P < 0.05 ), which was consistent with the results of the miRNA microarray. The enrichment analysis showed that baicalin might regulate the DNA-templated proliferation, DNA-templated transcription, p53 signaling pathway, etc., of MCF-7 breast cancer cells through miRNA. Conclusion. Baicalin inhibits the proliferation of breast cancer cells. It may achieve antitumor effects through regulating microRNAs so as to affect the DNA replication (such as cellular response to DNA damage stimulus and DNA binding), RNA transcription (such as regulation of transcription, DNA-templated, transcription from RNA polymerase II promoter, and transcription factor binding), protein synthesis (such as mRNA binding, Golgi apparatus, and protein complex), endocytosis, pathways in cancer, p53 signaling pathway, and so on.

scholarly journals Bafilomycin Prevented Curcumin-Induced Endoplasmic Reticulum (ER) Stress and Autophagy in MCF-7 Growth Hormone Positive (GH+) Breast Cancer Cells

Proceedings ◽  
2018 ◽  
Vol 2 (25) ◽  
pp. 1568
Author(s):  
Merve Karataş ◽  
Ajda Coker-Gurkan ◽  
Elif Damla Arisan ◽  
Pınar Obakan-Yerlikaya ◽  
Narcin Palavan-Unsal
Keyword(s):  
Breast Cancer ◽  
Growth Hormone ◽  
Endoplasmic Reticulum ◽  
Cell Viability ◽  
Er Stress ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Time Dependent ◽  
Dependent Manner ◽  
Mcf 7

Autocrine growth hormone (GH) induced cell proliferation, invasion-metastasis and drug resistance in breast cancer cells. Curcumin has an apoptotic effect on colon, melanoma, cervix, and breast cancer cells. Autophagy and endoplasmic reticulum (ER) stress are essential cellular processes activated under nutrient deprivation, pathogen infection and drug exposure. Our aim in this study is to investigate the time-dependent effect of curcumin on ER stress and autophagy and potential increase of curcumin efficiency by bafilomycin treatment. Autocrine GH expression triggered resistant profile against curcumin-induced cell viability loss in MCF-7 cells. However, this effect was prevented by the time-dependent manner in MCF-7 cells. In GH+ breast cancer cells bafilomycin increase curcumin-induced cell viability loss by MTT cell viability assay. In conclusion, autocrine GH-triggered curcumin resistance was overcome by autophagy inhibition condition by bafilomycin treatment in a dose-dependent manner in MCF-7 GH+ breast cancer cells.

scholarly journals CCL5 activation of CCR5 regulates cell metabolism to enhance proliferation of breast cancer cells

Open Biology ◽  
2016 ◽  
Vol 6 (6) ◽  
pp. 160122 ◽  
Author(s):  
Darrin Gao ◽  
Ramtin Rahbar ◽  
Eleanor N. Fish
Keyword(s):  
Breast Cancer ◽  
Glucose Uptake ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Tumour Cells ◽  
Mammary Tumour ◽  
Dependent Manner ◽  
Atp Production ◽  
Primary Mouse ◽  
Mcf 7

In earlier studies, we showed that CCL5 enhances proliferation and survival of MCF-7 breast cancer cells in an mTOR-dependent manner and we provided evidence that, for T cells, CCL5 activation of CCR5 results in increased glycolysis and enhanced ATP production. Increases in metabolic activity of cancer cells, specifically increased glycolytic activity and increased expression of glucose transporters, are associated with tumour progression. In this report, we provide evidence that CCL5 enhances the proliferation of human breast cancer cell lines (MDA-MB-231, MCF-7) and mouse mammary tumour cells (MMTV-PyMT), mediated by CCR5 activation. Concomitant with enhanced proliferation we show that CCL5 increases cell surface expression of the glucose transporter GLUT1, and increases glucose uptake and ATP production by these cells. Blocking CCL5-inducible glucose uptake abrogates the enhanced proliferation induced by CCL5. We provide evidence that increased glucose uptake is associated with enhanced glycolysis, as measured by extracellular acidification. Moreover, CCL5 enhances the invasive capacity of these breast cancer cells. Using metabolomics, we demonstrate that the metabolic signature of CCL5-treated primary mouse mammary tumour cells reflects increased anabolic metabolism. The implications are that CCL5–CCR5 interactions in the tumour microenvironment regulate metabolic events, specifically glycolysis, to promote tumour proliferation and invasion.

scholarly journals Effects of BET Inhibitor JQ1 and Interleukin-6 on Breast Cancer Cells

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.

Sign in / Sign up

Export Citation Format

Share Document