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

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.

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The Cytotoxic Properties of Baeckea frutescens Branches Extracts in Eliminating Breast Cancer Cells

Evidence-based Complementary and Alternative Medicine ◽

10.1155/2019/9607590 ◽

2019 ◽

Vol 2019 ◽

pp. 1-9 ◽

Cited By ~ 3

Author(s):

S. H. Shahruzaman ◽

M. F. Mustafa ◽

S. Ramli ◽

S. Maniam ◽

S. Fakurazi ◽

...

Keyword(s):

Breast Cancer ◽

Glucose Uptake ◽

Cancer Cells ◽

Breast Cancer Cells ◽

Glucose Consumption ◽

Uptake Assay ◽

Glucose Uptake Assay ◽

Baeckea Frutescens ◽

Mcf 7

Breast cancer is the leading cause of cancer death in women in over 100 countries worldwide and accounts for almost 1 in 4 cancer cases among women. Baeckea frutescens of the family Myrtaceae has been used in traditional medicine and is known to possess antibacterial, antipyretic, and cytoprotective properties. In this study, we investigated the role of Baeckea frutescens branches extracts against human breast cancer cells. Baeckea frutescens branches extracts were prepared using Soxhlet apparatus with solvents of different polarity. The selective cytotoxic activity and the glucose consumption rate of Baeckea frutescens branches extracts of various concentrations (20 to 160 ug/ml) at 24-, 48-, and 72-hour time points were studied using MTT and glucose uptake assay. The IC50 values in human breast cancer (MCF-7 and MDA-MB-231) and mammary breast (MCF10A) cell lines were determined. Apoptotic study using AO/PI double staining was performed using fluorescent microscopy. The glucose uptake was measured using 2-NBDG, a fluorescent glucose analogue. The phytochemical screening of major secondary metabolites in plants was performed. This study reports that Baeckea frutescens branches extracts showed potent selective cytotoxic activity against MCF-7 cells compared to MDA-MB-231 cells after 72 hours of treatment. Evidence of early apoptosis which includes membrane blebbing and chromatin condensation was observed after 72 hours of treatment with Baeckea frutescens branches extracts. Interestingly, for the glucose uptake assay, the inhibition was observed as early as 24 hours upon treatment. All Baeckea frutescens extracts showed the presence of major secondary metabolites such as tannin, triterpenoid, flavonoid, and phenol. However, alkaloid level was unable to be determined. The identification of Baeckea frutescens and its possible role in selectively inhibiting glucose consumption in breast cancer cells defines a new role of natural product that can be utilised as an effective agent that regulates metabolic reprogramming in breast cancer.

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

Cancer Nanotechnology ◽

10.1186/s12645-019-0052-1 ◽

2019 ◽

Vol 10 (1) ◽

Cited By ~ 3

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.

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

Molecular Endocrinology ◽

10.1210/me.2010-0294 ◽

2011 ◽

Vol 25 (1) ◽

pp. 72-82 ◽

Cited By ~ 35

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.

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

Endocrine Related Cancer ◽

10.1677/erc-09-0113 ◽

2009 ◽

Vol 16 (4) ◽

pp. 1185-1195 ◽

Cited By ~ 29

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.

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

10.1101/2021.10.28.466373 ◽

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.

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

Evidence-based Complementary and Alternative Medicine ◽

10.1155/2021/7624415 ◽

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.

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

Proceedings ◽

10.3390/proceedings2251568 ◽

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.

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

10.21203/rs.3.rs-1143331/v1 ◽

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.

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Emodin Inhibits the Proliferation of MCF-7 Human Breast Cancer Cells Through Activation of Aryl Hydrocarbon Receptor (AhR)

Frontiers in Pharmacology ◽

10.3389/fphar.2020.622046 ◽

2021 ◽

Vol 11 ◽

Author(s):

Ning Zhang ◽

Jiawen Wang ◽

Aimin Sheng ◽

Shuo Huang ◽

Yanyan Tang ◽

...

Keyword(s):

Breast Cancer ◽

Aryl Hydrocarbon Receptor ◽

Cancer Cells ◽

Human Breast Cancer ◽

Breast Cancer Cells ◽

Dependent Manner ◽

Human Breast Cancer Cells ◽

Human Breast ◽

Aryl Hydrocarbon ◽

Mcf 7

Natural products have proved to be a promising source for the development of potential anticancer drugs. Emodin, a natural compound from Rheum palmatum, is used to treat several types of cancers, including lung, liver, and pancreatic. However, there are few reports regarding its use in the treatment of breast cancer. Thus, the therapeutic effect and mechanism of emodin on MCF-7 human breast cancer cells were investigated in this study. Morphological observations and cell viability were evaluated to determine the anti-proliferation activity of emodin. Network pharmacology and molecular docking were performed to screen the potential targets. Western blot analysis was used to explore a potential antitumor mechanism. The results showed that emodin (50–100 μmol/L) could significantly inhibit the proliferation of MCF-7 cells in a time and dose-dependent manner. Furthermore, virtual screening studies indicated that emodin was a potent aryl hydrocarbon receptor (AhR) agonist in chemotherapy for breast cancer. Finally, when MCF-7 cells were treated with emodin (100 μmol/L) for 24 h, the AhR and cytochrome P450 1A1 (CYP1A1) protein expression levels were significantly upregulated compared with the control group. Our study indicated that emodin exhibited promising antitumor activity in MCF-7 cells, likely through activation of the AhR-CYP1A1 signaling pathway. These findings lay a foundation for the application of emodin in breast cancer treatment.

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Docosahexaenoic acid monoglyceride induces apoptosis and autophagy in breast cancer cells via lipid peroxidation-mediated endoplasmic reticulum stress

10.21203/rs.3.rs-35529/v2 ◽

2021 ◽

Author(s):

Tian-tian Wang ◽

Yong Yang ◽

Feng Wang ◽

Wen-ge Yang ◽

Jin-jie Zhang ◽

...

Keyword(s):

Breast Cancer ◽

Endoplasmic Reticulum ◽

Docosahexaenoic Acid ◽

Growth Inhibition ◽

Er Stress ◽

Cancer Cells ◽

Breast Cancer Cells ◽

Control Group ◽

Dependent Manner ◽

Mcf 7

Abstract Epidemiologic and pre-clinical studies have shown that marine n-3 polyunsaturated fatty acids (n-3 PUFAs) elicit promising chemoprevention against breast cancer. Docosahexaenoic acid monoglyceride (MAG-DHA), a docosahexaenoic acid sn-1-monoacylglyceroldoes not required pancreatic lipase to be absorbed, eliciting a better bioavailability when compared with other formulations such as DHA-free fatty acid, DHA-triglycerol, or DHA-ethyl ester. However, the anti-cancer actions and underlying mechanisms of MAG-DHA on breast cancer remain to be assessed. In this study, MAG-DHA induced significant growth inhibition in MCF-7 and MDA-MB-231 breast cancer cells in a dose-dependent manner. MAG-DHA treatment (80μM) led to 83.8% and 94.3% growth inhibition between MCF-7 and MDA-MB-231 cells, respectively. MAG-DHA-induced growth inhibition was tightly associated with apoptosis, as evidenced by increased active forms of caspase-3, poly (ADP-ribose) polymerase (PARP) and caspase-12. In particular, MAG-DHA-induced apoptosis was triggered by oxidative stress-mediated endoplasmic reticulum (ER) stress, as evidenced by activation of the PERK-eIF2α pathway in ER. MAG-DHA treatment also strongly suppressed the growth of E0771 murine breast cancer xenografts, significant differences of tumor volume were found between MAG-DHA group (0.271 cm3) and control group (0.875cm3) after 15 daily MAG-DHA treatments. The in vitro anti-breast cancer mechanism of MAG-DHA was supported by the in vivo xenograft model. In addition, MAG-DHA-induced ER stress concomitantly triggered autophagy in these cancer cells, and the induction of autophagy suppressed its ability to induce apoptotic cell death. Our data suggested that MAG-DHA as dietary supplement, in combination with autophagy inhibitors may be a useful therapeutic strategy in treating breast cancer.

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