Statin-Induced Inhibition of MCF-7 Breast Cancer Cell Proliferation is Related to Cell Cycle Arrest and Apoptotic and Necrotic Cell Death Mediated by an Enhanced Oxidative Stress

2008 ◽  
Vol 26 (7) ◽  
pp. 698-707 ◽  
Author(s):  
Claudia A. Sánchez ◽  
Emma Rodríguez ◽  
Elvira Varela ◽  
Estrella Zapata ◽  
Araceli Páez ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Oxidative Stress ◽  
Cell Cycle ◽  
Cell Proliferation ◽  
Necrotic Cell Death ◽  
Cancer Cell Proliferation ◽  
Necrotic Cell ◽  
Breast Cancer Cell Proliferation ◽  
Cycle Arrest ◽  
Mcf 7

scholarly journals GLUTATHIONE AND GLUTAREDOXIN IN ROSCOVITINE-MEDIATED INHIBITION OF BREAST CANCER CELL PROLIFERATION

2017 ◽  
Vol 72 (4) ◽  
pp. 261-267 ◽  
Author(s):  
E. V. Shakhristova ◽  
E. A. Stepovaya ◽  
O. L. Nosareva ◽  
E. V. Rudikov ◽  
V. V. Novitsky
Keyword(s):  
Breast Cancer ◽  
Cell Cycle ◽  
Cell Proliferation ◽  
Protein Kinase ◽  
Breast Cancer Cell ◽  
Cancer Cell Proliferation ◽  
Breast Cancer Cell Proliferation ◽  
Dependent Protein Kinase ◽  
Dependent Protein ◽  
Mcf 7

Background: Breast tumors are number one cause of cancer morbidity and mortality among women around the world, and Russia is not an exception. Many proteins that control proliferation of immortalized cells are redox-regulated, which is essential for modulating cellular proliferative activity, especially during tumor growth. Studying the role of glutaredoxin and glutathione in cell cycle phase distribution will allow not only to identify the molecular targets regulating cell proliferation, but also to develop methods of diagnosis and targeted therapy of socially sensitive diseases, including breast cancer, in the future.Aims: To evaluate the role of glutathione and glutaredoxin in the molecular mechanisms regulating MCF-7 breast cancer cell proliferation under the effects of roscovitine, a cyclin-dependent protein kinase inhibitor.Materials and methods: The MCF-7 cell line (human breast adenocarcinoma) was used in the study. The cell culture was incubated in the presence and absence of roscovitine in the final concentration of 20 µmol for 18 h. The production of reactive oxygen species, the distribution of cells between cell cycle phases and the amount of Annexin V positive cells were determined using flow cytometry. The concentrations of total, reduced and oxidized glutathione, protein SH groups and protein-bound glutathione were measured by spectrophotometry. The levels of glutaredoxin, cyclin E and cyclin-dependent protein kinases were estimated by Western blotting with monoclonal antibodies.Results: The effects of roscovitine in the MCF-7 cells resulted in cell cycle arrest in G2/М phases with the decreased levels of cyclin E and cyclin-dependent protein kinase 2. It was accompanied by activation of programmed cell death. In tumor cells incubated in the presence of roscovitine, oxidative stress was triggered, which was accompanied by the elevated generation of reactive oxygen species, the decrease in the concentration of reduced glutathione, and the rise in the level of glutaredoxin. It contributed to the increase in protein glutathionylation against the backdrop of the decreased SH group concentration.Conclusions: Breast cancer cell proliferation under the effects of roscovitine is reduced following not only the decrease in the cyclin level and cyclin-dependent protein kinase activity, but also the shift in the intracellular oxidant/antioxidant ratio. Roscovitine-induced oxidative stress in the MCF-7 cells contributed to protein glutathionylation with the changes in the protein structure and functions. It results in impaired cell cycle progression, indicating a possibility to regulate cellular proliferation through modulating functional properties of redox-dependent proteins using the glutathione/glutaredoxin system.

scholarly journals Protein carbonylation as a possible way to modulate breast cancer cell proliferation

2019 ◽  
Vol 17 (6) ◽  
pp. 78-83
Author(s):  
E. V. Shakhristova ◽  
E. A. Stepovaya ◽  
A. A. Sadykova ◽  
V. V. Novitsky
Keyword(s):  
Breast Cancer ◽  
Cell Cycle ◽  
Cell Proliferation ◽  
Cancer Cell ◽  
Breast Cancer Cell ◽  
Redox Status ◽  
Oxidative Modification ◽  
Cancer Cell Proliferation ◽  
Breast Cancer Cell Proliferation ◽  
Cycle Arrest

Introduction.High rates of cancer incidence and mortality worldwide dictate the necessity of developing new methodological approaches in understanding the molecular mechanisms of cancer progression associated with intracellular redox regulation imbalance.The objectiveof the study was to evaluate the role of protein carbonylation in regulating breast cancer cell proliferation under redox status modulation.Materials and Methods. In the intact breast cancer cells and in the cells cultured under redox status modulation using 5mM N-ethylmaleimide (an - SH group blocker) and 5 Mm 1,4-dithioerythritol (a thiol group protector), the concentration of thioredoxin and its carbonylated form was measured using Western blot analysis. The activity of thioredoxin reductase and the level of protein carbonyl derivatives were determined using spectrophotometry. Cell cycle phase distribution was evaluated by flow cytometry.Results and Discussion. Under the effect of N-ethylmaleimide, cell cycle arrest in the S-phase was confirmed by oxidative modification of proteins, including thioredoxin carbonylation. When culturing MCF-7 cells in the presence of 1,4-dithioerythritol, cell cycle arrest in the G0/G1 phases was associated with a rise in the concentrations of reduced thioredoxin and glutathione forms.Conclusion.The thioredoxin system and oxidative modification of proteins are involved in redox-dependent modulation of breast cancer cell proliferation. Studies in the area of redox proteomics offer great potential to seek molecular targets of malignant transformation of breast cells.

scholarly journals Estrogen-Like Properties of Fluorotelomer Alcohols as Revealed by MCF-7 Breast Cancer Cell Proliferation

2006 ◽  
Vol 114 (1) ◽  
pp. 100-105 ◽  
Author(s):  
Marleen Maras ◽  
Caroline Vanparys ◽  
Frederik Muylle ◽  
Johan Robbens ◽  
Urs Berger ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cell Proliferation ◽  
Cancer Cell ◽  
Breast Cancer Cell ◽  
Cancer Cell Proliferation ◽  
Breast Cancer Cell Proliferation ◽  
Fluorotelomer Alcohols ◽  
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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 Radiation-Triggered NF-κB Activation is Responsible for the Angiogenic Signaling Pathway and Neovascularization for Breast Cancer Cell Proliferation and Growth

2012 ◽  
Vol 6 ◽  
pp. BCBCR.S9592 ◽  
Author(s):  
Hui Yu ◽  
Sumathy Mohan ◽  
Mohan Natarajan
Keyword(s):  
Breast Cancer ◽  
Cell Proliferation ◽  
Endothelial Cells ◽  
Radiation Exposure ◽  
Signaling Pathway ◽  
Cancer Cell ◽  
Breast Cancer Cell ◽  
Cancer Cell Proliferation ◽  
Breast Cancer Cell Proliferation ◽  
Mcf 7

Tumors require blood supply to survive, grow, and metastasize. This involves the process of angiogenesis signaling for new blood vessel growth into a growing tumor mass. Understanding the mechanism of the angiogenic signaling pathway and neovascularization for breast cancer cell proliferation and growth would help to develop molecular interventions and achieve disease free survival. Our hypothesis is that the surviving cancer cell(s) after radiotherapy can initiate angiogenic signaling pathway in the neighboring endothelial cells resulting in neovascularization for breast cancer cell growth. The angiogenic signaling pathway is initiated by angiogenic factors, VEGF and FGF-2, through activation of a transcriptional regulator NF-κB, which in turn is triggered by therapeutic doses of radiation exposure Human breast adenocarcinoma cells (MCF-7 cells) were exposed to Cesium-137 (137Cs) γ rays to a total dose of 2 Gy at a dose rate of 1.03 Gy/min. The results of mobility shift assay showed that radiation at clinical doses (2 Gy) could induce NF-κB DNA-binding activity. Then, we examined the communication of angiogenic signals from irradiated MCF-7 cells to vascular endothelial cells. At the protein level, the western blot showed induction of angiogenic factors VEGF and FGF-2 in MCF-7 cells irradiated with 2 Gy. Inhibition of NF-κB activation attenuated VEGF and FGF-2 levels. These factors are secreted into the medium. The levels of VEGF and FGF-2 in the extra cellular medium were both increased, after 2 Gy exposures. We also observed corresponding expression of VEGFR2 and FGFR1 in non-irradiated endothelial cells that were co-cultured with irradiated MCF-7 cells. In support of this, in vitro tube formation assays provided evidence that irradiated MCF-7 cells transmit signals to potentiate cultured non-irradiated endothelial cells to form tube networks, which is the hallmark of neovascularization. Inhibition of NF-κB activation attenuated irradiated MCF-7-induced tube network formation. The data provide evidence that the radiation exposure is responsible for tumor growth and maintenance by inducing an angiogenic signaling pathway through activation of NF-κB.

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