scholarly journals Causes and Consequences of A Glutamine Induced Normoxic HIF1 Activity for the Tumor Metabolism

2019 ◽  
Vol 20 (19) ◽  
pp. 4742 ◽  
Author(s):  
Matthias Kappler ◽  
Ulrike Pabst ◽  
Claus Weinholdt ◽  
Helge Taubert ◽  
Swetlana Rot ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Ascorbic Acid ◽  
Amino Acid ◽  
Tumor Cells ◽  
Cancer Cell ◽  
Breast Cancer Cell ◽  
Glutamine Metabolism ◽  
Dependent Manner ◽  
Acetyl Coa ◽  
Hypoxic Conditions

The transcription factor hypoxia-inducible factor 1 (HIF1) is the crucial regulator of genes that are involved in metabolism under hypoxic conditions, but information regarding the transcriptional activity of HIF1 in normoxic metabolism is limited. Different tumor cells were treated under normoxic and hypoxic conditions with various drugs that affect cellular metabolism. HIF1α was silenced by siRNA in normoxic/hypoxic tumor cells, before RNA sequencing and bioinformatics analyses were performed while using the breast cancer cell line MDA-MB-231 as a model. Differentially expressed genes were further analyzed and validated by qPCR, while the activity of the metabolites was determined by enzyme assays. Under normoxic conditions, HIF1 activity was significantly increased by (i) glutamine metabolism, which was associated with the release of ammonium, and it was decreased by (ii) acetylation via acetyl CoA synthetase (ACSS2) or ATP citrate lyase (ACLY), respectively, and (iii) the presence of L-ascorbic acid, citrate, or acetyl-CoA. Interestingly, acetylsalicylic acid, ibuprofen, L-ascorbic acid, and citrate each significantly destabilized HIF1α only under normoxia. The results from the deep sequence analyses indicated that, in HIF1-siRNA silenced MDA-MB-231 cells, 231 genes under normoxia and 1384 genes under hypoxia were transcriptionally significant deregulated in a HIF1-dependent manner. Focusing on glycolysis genes, it was confirmed that HIF1 significantly regulated six normoxic and 16 hypoxic glycolysis-associated gene transcripts. However, the results from the targeted metabolome analyses revealed that HIF1 activity affected neither the consumption of glucose nor the release of ammonium or lactate; however, it significantly inhibited the release of the amino acid alanine. This study comprehensively investigated, for the first time, how normoxic HIF1 is stabilized, and it analyzed the possible function of normoxic HIF1 in the transcriptome and metabolic processes of tumor cells in a breast cancer cell model. Furthermore, these data imply that HIF1 compensates for the metabolic outcomes of glutaminolysis and, subsequently, the Warburg effect might be a direct consequence of the altered amino acid metabolism in tumor cells.

scholarly journals Productive Infection of Human Breast Cancer Cell Lines with Human Cytomegalovirus (HCMV)

Pathogens ◽  
2021 ◽  
Vol 10 (6) ◽  
pp. 641
Author(s):  
Kaitlin M. Branch ◽  
Erica C. Garcia ◽  
Yin Maggie Chen ◽  
Matthew McGregor ◽  
Mikayla Min ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Tumor Cells ◽  
Cell Lines ◽  
Cancer Cell ◽  
Breast Cancer Cell ◽  
Breast Tumor ◽  
Cancer Cell Lines ◽  
Breast Cancer Cell Lines ◽  
Human Breast ◽  
Breast Tumor Cells

Breast cancer is the leading cause of cancer deaths among women worldwide. There are many known risk factors for breast cancer, but the role of infectious disease remains unclear. Human cytomegalovirus (HCMV) is a widespread herpesvirus that usually causes little disease. Because HCMV has been detected in breast tumor biopsy samples and is frequently transmitted via human breast milk, we investigated HCMV replication in breast tumor cells. Four human breast cancer cell lines with different expression profiles for the key diagnostic markers of the estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2), were infected with a bacterial artificial chromosome-derived HCMV clinical strain TB40/E tagged with green fluorescent protein (GFP). Fluorescence microscopy confirmed that all four breast cancer cell lines supported virus entry. RNA was isolated from infected cells and the expression of immediate early (UL123), early (UL54), and late (UL111A) genes was confirmed using PCR. Viral proteins were detected by immunoblotting, and viral progeny were produced during the infection of breast tumor cells, as evidenced by subsequent infection of fibroblasts with culture supernatants. These results demonstrate that breast tumor cells support productive HCMV infection and could indicate that HCMV replication may play a role in breast cancer progression.

scholarly journals Potassium increases the antitumor effects of ascorbic acid in breast cancer cell lines in vitro

2016 ◽  
Vol 11 (6) ◽  
pp. 4224-4234 ◽  
Author(s):  
GIOVANNI VANNI FRAJESE ◽  
MONICA BENVENUTO ◽  
MASSIMO FANTINI ◽  
ELENA AMBROSIN ◽  
PAMELA SACCHETTI ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Ascorbic Acid ◽  
Cell Lines ◽  
Cancer Cell ◽  
Breast Cancer Cell ◽  
Cancer Cell Lines ◽  
Breast Cancer Cell Lines ◽  
Antitumor Effects

The Effect of Sirtuin 2 (Sirt2) Overexpressing Bone Marrow Mesenchymal Stem Cells on the Growth of Human Epidermal Growth Factor Receptor 2 (Her-2) Breast Cancer Cells and Its Mechanism

2021 ◽  
Vol 11 (4) ◽  
pp. 778-785
Author(s):  
Xiaolin Chen ◽  
Yan Wang ◽  
Sunlu Jiang
Keyword(s):  
Breast Cancer ◽  
Flow Cytometry ◽  
Nk Cells ◽  
Tumor Cells ◽  
Cancer Cell ◽  
Breast Cancer Cell ◽  
Caspase 3 ◽  
Tumor Bearing ◽  
Her 2 ◽  
Ifn Γ

Our study investigates the effect of high expression of Sirt2 in MSCs (MSCs-Sirt2) on Her-2 breast cancer cell proliferation. A mouse subcutaneous xenograft tumor model was established and MSCssirt2 analysis was performed on nude mice. TUNEL staining, flow cytometry, western-blot, real-time PCR and immunohistochemistry were used to detect cancer cell apoptosis. The number of NK cells infiltrated by flow cytometry detected the tumor tissue of tumor-bearing mice, and its killing activity on tumor-bearing mice was detected by isotope labeling and release method. The levels of TNF-α, IFN-γ, IL-8, IL-6 and IL-10 were detected by ELISA. Caspase-3 level was decreased in the MSCs group (P <0.01) while increased in the MSCs-sirt2 group (P <0.001). However, PCNA expression showed an opposite profile in the Her-2 group and MSCs-sirt2 group compared to Caspase-3 level (P <0.01). The tumor volume and weight in the MSCs-sirt2 group was significantly reduced (P < 0.01), while increased in the MSCs group significantly (P < 0.05). The number of Ki-67-positive tumor cells in MSCs-sirt2 group was significantly reduced (P <0.01) and increased in MSCs group (P < 0.001) with oppositive number of TUNEL-positive tumor cells in the MSCs-sirt2 group and MSCs group (P <0.01). IFN-γ level showed an upward trend (P <0.001). The NK cell toxicity of MSCs-Sirt2 group was significantly higher (P <0.001). MSCs-Sirt2 has an inhibitory effect on Her-2 breast cancer cell growth by enhancing the local inflammatory response of NK cells.

scholarly journals Exendin-4, a Glucagonlike Peptide-1 Receptor Agonist, Attenuates Breast Cancer Growth by Inhibiting NF-κB Activation

Endocrinology ◽  
2017 ◽  
Vol 158 (12) ◽  
pp. 4218-4232 ◽  
Author(s):  
Chikayo Iwaya ◽  
Takashi Nomiyama ◽  
Shiho Komatsu ◽  
Takako Kawanami ◽  
Yoko Tsutsumi ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Diabetes Mellitus ◽  
Cell Proliferation ◽  
Cancer Cell ◽  
Breast Cancer Cell ◽  
Cancer Tissue ◽  
Dependent Manner ◽  
Cancer Cell Proliferation ◽  
Breast Cancer Cell Proliferation ◽  
Mcf 7

Abstract Incretin therapies have received much attention because of their tissue-protective effects, which extend beyond those associated with glycemic control. Cancer is a primary cause of death in patients who have diabetes mellitus. We previously reported antiprostate cancer effects of the glucagonlike peptide-1 (GLP-1) receptor (GLP-1R) agonist exendin-4 (Ex-4). Breast cancer is one of the most common cancers in female patients who have type 2 diabetes mellitus and obesity. Thus, we examined whether GLP-1 action could attenuate breast cancer. GLP-1R was expressed in human breast cancer tissue and MCF-7, MDA-MB-231, and KPL-1 cell lines. We found that 0.1 to 10 nM Ex-4 significantly decreased the number of breast cancer cells in a dose-dependent manner. Although Ex-4 did not induce apoptosis, it attenuated breast cancer cell proliferation significantly and dose-dependently. However, the dipeptidyl peptidase-4 inhibitor linagliptin did not affect breast cancer cell proliferation. When MCF-7 cells were transplanted into athymic mice, Ex-4 decreased MCF-7 tumor size in vivo. Ki67 immunohistochemistry revealed that breast cancer cell proliferation was significantly reduced in tumors extracted from Ex-4-treated mice. In MCF-7 cells, Ex-4 significantly inhibited nuclear factor κB (NF-κB ) nuclear translocation and target gene expression. Furthermore, Ex-4 decreased both Akt and IκB phosphorylation. These results suggest that GLP-1 could attenuate breast cancer cell proliferation via activation of GLP-1R and subsequent inhibition of NF-κB activation.

scholarly journals p53–GSDME Elevation: A Path for CDK7 Inhibition to Suppress Breast Cancer Cell Survival

2021 ◽  
Vol 8 ◽  
Author(s):  
Yueyuan Wang ◽  
Jingyu Peng ◽  
Xuguang Mi ◽  
Ming Yang
Keyword(s):  
Breast Cancer ◽  
Cell Proliferation ◽  
Cell Survival ◽  
Cancer Cell ◽  
Breast Cancer Cell ◽  
Colony Formation ◽  
Dependent Manner ◽  
Cancer Cell Proliferation ◽  
Breast Cancer Cell Proliferation ◽  
Cancer Cell Survival

Higher cyclin-dependent kinase (CDK7) expression is a character of breast cancer and indicates poor prognosis. Inhibiting CDK7 exhibited effective cancer cell suppression which implies the potential of CDK7 inhibition to be a method for anti-cancer treatment. Our study aimed to explore a novel mechanism of CDK7 inhibition for suppressing breast cancer cell survival. Here, we proved inhibiting CDK7 repressed breast cancer cell proliferation and colony formation and increased the apoptotic cell rate, with p53 and GSDME protein level elevation. When p53 was suppressed in MCF-7 cells, the decline of GSDME expression and associated stronger proliferation and colony formation could be observed. Since downregulation of GSDME was of benefit to breast cancer cells, p53 inhibition blocked the elevation of GSDME induced by CDK7 inhibition and retrieved cells from the tumor suppressive effect of CDK7 inhibition. Therefore, CDK7 inhibition exerted a negative effect on breast cancer cell proliferation and colony formation in a p53–GSDME dependent manner. These results revealed the CDK7–p53–GSDME axis could be a pathway affecting breast cancer cell survival.

scholarly journals An Antioxidant Polysaccharide from Ganoderma lucidum Induces Apoptotic Activity in Breast Cancer Cell Line 

2022 ◽  
Author(s):  
Md. Moyen Uddin Pk ◽  
Rumana Pervin ◽  
Mohammad Shahangir Biswas ◽  
Matiar Rahman
Keyword(s):  
Breast Cancer ◽  
Cell Line ◽  
Cancer Cell ◽  
Breast Cancer Cell ◽  
Breast Cancer Cell Line ◽  
Ganoderma Lucidum ◽  
Cancer Cell Line ◽  
Dependent Manner ◽  
Apoptotic Activity ◽  
Mcf 7

The purpose of this study is to elucidate the apoptotic activity of Ganoderma lucidum  polysaccharide (GLP) in a human breast cancer cell line MCF-7 in vitro.  According to DPPH assay, GLP showed a good antioxidant (IC 50  value is 202.4 µg/mL). Based on MTT assay, the results showed that GLP inhibits MCF-7 cells proliferation in a dose- and time- dependent manner (p<0.001). IC 50   values of the cytotoxicity of GLP and doxorubin  were 110.907 µg/mL and 58.206 µg/mL respectively. The results from the flow cytometry indicated that GLP could induce apoptotic activity through inducing the up-regulation of the Bax and Caspase-9 and the down-regulation of the BcL-2 in MCF-7 cells. At 2×IC 50 , GLP increased the early-apoptotic and dead cells of MCF-7 from 18.23% to 34.76% and 8.45% to16.34% respectively. In conclusion, the GLP shows anticancer activity against MCF-7 through preventing the proliferation and inducing the apoptosis of MCF-7 cells. Our data provide the potential molecular targets in cancer prevention and reveal the key barriers in the current anticancer drugs development.

Silibinin Inhibit Cell Migration through Downregulation of RAC1 Gene Expression in Highly Metastatic Breast Cancer Cell Line

Drug Research ◽  
2020 ◽  
Vol 70 (10) ◽  
pp. 478-483
Author(s):  
Hamed Esmaeil Lashgarian ◽  
Vahid Adamii ◽  
Vajihe Ghorbanzadeh ◽  
Leila Chodari ◽  
Fayze Kamali ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cell Line ◽  
Tumor Cells ◽  
Cancer Cell ◽  
Breast Cancer Cell ◽  
Breast Cancer Cell Line ◽  
Cancer Cell Line ◽  
Migration And Invasion ◽  
And Migration ◽  
Proliferation And Migration

Abstract Background Triple negative breast cancer is the most invasive breast cancer subtype and possesses poor prognosis and survival. Rho GTPase famil, especially Rac1 participates in a number of signaling events in cells with crucial roles in malignancy, migration and invasion of tumor cells. Silibinin, a flavonoid antioxidant from milk thistle has attracted attention in the recent decades for chemoprevention and chemotherapy of tumor cells. In this study, the effect of silibinin on the migration capacity of MDA-MB-231 cells, a highly metastatic human breast cancer cell line was investigated by evaluation of Rac1 expression. Method MTT wound healing and transwell assays were performed to evaluate the effects of silibinin on proliferation and migration of MDA-MB-231 cells. In addition, the influence of the silibinin on the expression of Rac1mRNAs was assessed by RT-PCR. Results Results indicated significant dose-dependent inhibitory effect of silibinin on proliferation and migration of MDA-MB-231 cells. It significantly inhibited the expression of Rac1 mRNA. Conclusion In conclusion, the results demonstrate that the silibinin can be used as an experimental therapeutic for the management of TNBC metastatic cancer.

Preclinical evaluation of PARP inhibition in breast cancer: Comparative effectiveness of olaparib and iniparib.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 1042-1042 ◽  
Author(s):  
Maura B. Cotter ◽  
Aisling Pierce ◽  
Patricia M. McGowan ◽  
Louise Flanagan ◽  
Cecily Quinn ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cell Lines ◽  
Cancer Cell ◽  
Breast Cancer Cell ◽  
Staining Intensity ◽  
Cancer Cell Lines ◽  
Parp Inhibition ◽  
Breast Cancer Cell Lines ◽  
Main Function ◽  
Dependent Manner

1042 Background: The main function of PARP1 is repair of single-strand DNA. Phase I/II clinical trials have shown that the PARP inhibitor, olaparib has efficacy in BRCA1/2-related breast cancer. Due to the similarities between BRCA1/2-associated and triple negative breast cancer (TNBC), we hypothesise that TNBC may also be sensitive to PARP inhibition. In order to assess this we addressed the effects of 2 PARP/PARP-like inhibitors, on a panel of breast cancer cell lines. Methods: PARP1 was measured by immunohistochemistry in 101 TNBC and 116 non-TN cancers. Comparative growth inhibitory capacity of olaparib and iniparib was evaluated using cell viability (MTT) and colony formation assays in 12 breast cancer cell lines (TN=7, non-TN=5). Results: Using immunohistochemistry, PARP1 staining was predominantly nuclear with some cytoplasmic staining. High staining intensity for PARP1 was found more frequently in ER-negative (p = 0.001), in high grade (p = 0.013) and in Ki67-positive ( p = 0.003) samples. Potentially important was the finding that high PARP1 staining intensity was detected more frequently in TN than non-TN samples (p = 0.0001). IC50 concentrations across 12 cell lines ranged from 3.7-31 µM for olaparib and 13-70 µM for iniparib. No difference in sensitivity was observed between the TN and non-TN cell lines (by MTT). Olaparib also reduced the ability of cells to form colonies with IC50 values ranging from <0.01-2.5 µM. Addition of the CDKI inhibitor CDK1i (Calbiochem) to olaparib resulted in formation of significantly fewer colonies compared with either inhibitor alone, in a cell line dependent manner. Conclusions: Our results suggest that although PARP1 is expressed in the majority of breast cancer, significantly higher staining intensity was found in TN than non-TN samples. Furthermore, our work suggests that olaparib is a more potent inhibitor of the in vitro growth of breast cancer cells than iniparib. Combined inhibition of PARP1 with olaparib and CDK1 with CDK1i may be a way forward for the treatment of TNBC. Acknowledgement: The authors thank SFI (SRC award, 08/SRC/B1410 MTCI) for funding this work.

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