scholarly journals Primate-specific oestrogen-responsive long non-coding RNAs regulate proliferation and viability of human breast cancer cells

Open Biology ◽  
2016 ◽  
Vol 6 (12) ◽  
pp. 150262 ◽  
Author(s):  
Chin-Yo Lin ◽  
Erica L. Kleinbrink ◽  
Fabien Dachet ◽  
Juan Cai ◽  
Donghong Ju ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cell Viability ◽  
Cancer Cells ◽  
Human Breast Cancer ◽  
Oestrogen Receptor ◽  
Breast Cancer Cells ◽  
Signalling Pathways ◽  
Human Breast Cancer Cells ◽  
Human Breast ◽  
Non Coding Rnas

Long non-coding RNAs (lncRNAs) are transcripts of a recently discovered class of genes which do not code for proteins. LncRNA genes are approximately as numerous as protein-coding genes in the human genome. However, comparatively little remains known about lncRNA functions. We globally interrogated changes in the lncRNA transcriptome of oestrogen receptor positive human breast cancer cells following treatment with oestrogen, and identified 127 oestrogen-responsive lncRNAs. Consistent with the emerging evidence that most human lncRNA genes lack homologues outside of primates, our evolutionary analysis revealed primate-specific lncRNAs downstream of oestrogen signalling. We demonstrate, using multiple functional assays to probe gain- and loss-of-function phenotypes in two oestrogen receptor positive human breast cancer cell lines, that two primate-specific oestrogen-responsive lncRNAs identified in this study (the oestrogen-repressed lncRNA BC041455, which reduces cell viability, and the oestrogen-induced lncRNA CR593775, which increases cell viability) exert previously unrecognized functions in cell proliferation and growth factor signalling pathways. The results suggest that oestrogen-responsive lncRNAs are capable of altering the proliferation and viability of human breast cancer cells. No effects on cellular phenotypes were associated with control transfections. As heretofore unappreciated components of key signalling pathways in cancers, including the MAP kinase pathway, lncRNAs hence represent a novel mechanism of action for oestrogen effects on cellular proliferation and viability phenotypes. This finding warrants further investigation in basic and translational studies of breast and potentially other types of cancers, has broad relevance to lncRNAs in other nuclear hormone receptor pathways, and should facilitate exploiting and targeting these cell viability modulating lncRNAs in post-genomic therapeutics.

Molecular mechanisms of oestrogen action on growth of human breast cancer cells in culture

2012 ◽  
Vol 9 (1) ◽  
Author(s):  
Philippa D. Darbre
Keyword(s):  
Breast Cancer ◽  
Cell Growth ◽  
Cancer Cells ◽  
Human Breast Cancer ◽  
Oestrogen Receptor ◽  
Breast Cancer Cells ◽  
Molecular Mechanisms ◽  
Signalling Pathways ◽  
Human Breast Cancer Cells ◽  
Human Breast

AbstractGrowth responses to oestrogen can be reproducibly obtained using a selection of oestrogen-receptor-containing human breast cancer cell lines, and molecular mechanisms have been shown to include modulation to growth factor/receptor/signalling pathways, cell-cycle proteins, apoptosis, differentiation, adhesion, motility and migration. Considerable progress has been made in understanding the molecular basis of oestrogen action on gene expression through the ligand-activated transcription factors human oestrogen receptor α (ERα) and ERβ and the resulting effects on global gene expression patterns, but the full profile of coordination of the alterations, which brings about changes in cell growth through genomic and non-genomic mechanisms remain to be fully elucidated. Oestrogen regulation of cell growth involves a complex cross-talk between oestrogen receptor and growth factor signalling pathways such that inhibition of one pathway may lead to stimulation of another, which may explain the remarkable ability of human breast cancer cells to escape from any mode of imposed growth inhibition be it oestrogen deprivation or administration of antioestrogen. Although studies on cell growth have focused to date on the effects of physiological oestrogens, many hundreds of environmental chemicals with oestrogenic properties have now been measured in the human breast. Whether or not the weight of evidence eventually establishes any causal link of complex mixtures of environmental oestrogenic chemicals with breast cancer, the presence of so many oestrogenic chemicals in the breast must influence resulting oestrogenic responses, and the impact of this additional oestrogenic burden needs to be taken into account in future studies on growth regulation of human breast cancer cells.

Chitosan conjugation: A facile approach to enhance the cell viability of LaF 3 :Yb,Er upconverting nanotransducers in human breast cancer cells

2015 ◽  
Vol 121 ◽  
pp. 302-308 ◽  
Author(s):  
Sethuraman Gayathri ◽  
Oriparambil Sivaraman Nirmal Ghosh ◽  
P. Sudhakara ◽  
Annamraju Kasi Viswanath
Keyword(s):  
Breast Cancer ◽  
Cell Viability ◽  
Cancer Cells ◽  
Human Breast Cancer ◽  
Breast Cancer Cells ◽  
Human Breast Cancer Cells ◽  
Human Breast

Benzene-poly-carboxylic acids complex with Cis-diammineplatinum (II) dichloride (BP-C1), a novel anticancer agent, induces apoptosis in human breast cancer cells through caspase activation.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. e12029-e12029
Author(s):  
Fuad Fares ◽  
Basem Fares ◽  
Stig Larsen ◽  
Steen Lindkair-Jensen
Keyword(s):  
Breast Cancer ◽  
Cell Viability ◽  
Cancer Cells ◽  
Human Breast Cancer ◽  
Breast Cancer Cells ◽  
Human Breast Cancer Cells ◽  
Human Breast ◽  
Caspase Activation ◽  
Induction Of Apoptosis ◽  
Apoptotic Genes

e12029 Background: Breast cancer is the most frequent malignancy in women in western countries and despite progress in the treatment options surgery, radiation, chemotherapy and hormonal therapy it is still the leading cause of cancer death. BP-C1 is a novel anti-cancer complex of benzol-polycarbonic acids with ammonium-platinum salt developed by Meabco ltd, Denmark. Methods: In the present study, the effect of BP-C1 on growth of human breast cancer cells, MCF7 and T47D, was studied. Cells were exposed to different doses of BP-C1, 100-1000 µg/ml, and cell viability, toxicity (LDH release), cell cycle, apoptosis, caspase activation and gene expression were examined. Results: No toxicity was observed. Exposure of the cells to BP-C1 for 48h, significantly (P<0.001) reduced cell viability by approxematly 90% with IC50 of 400 µg/ml. In cell cycle studies cells were accumulated in sub-G1 phase, which may indicate induction of apoptosis. Annexin 5 assay demonstrated that BP-C1 induces apoptosis of MCF-7 and T47D cell by 65% and 34%, respectively, after 48h of treatment. Detection of caspases by western blot analysis revealed that BP-C1 activates caspase 8 and caspase 9. Moreover, gene expression experiments following BP-C1 treatment and using the Applied Biosystems TaqMan Array Plates indicated that BP-C1 caused an increase in the the expression of pro-apoptotic genes; CASP8AP2, TNFRSF21, RELB, NFKB2, BIRC8 and FADD when compared to the expression level of the House keeping genes, HPRT1 and GAPDH. On the other hand, lower levels of mRNA transcripts of the inhibitory apoptotic genes; BCL2L2 and XIAP were detected. Conclusions: These results may indicate that BP-C1 reduced cell viability of human cancer cells by a unigue induction of apoptosis through activation of the extrinsic (death receptors) and the intrinsic (mitochondrion) apoptotic pathways. These findings may lead to the development of new therapeutic strategies for treatment of cancer using BP-C1 or analogs.

scholarly journals Serotonin activates glycolysis and mitochondria biogenesis in human breast cancer cells through activation of the Jak1/STAT3/ERK1/2 and adenylate cyclase/PKA, respectively

2019 ◽  
Vol 122 (2) ◽  
pp. 194-208 ◽  
Author(s):  
Mauro Sola-Penna ◽  
Larissa P. Paixão ◽  
Jessica R. Branco ◽  
Alan C. Ochioni ◽  
Jamille M. Albanese ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Adenylyl Cyclase ◽  
Cancer Cells ◽  
Mitochondrial Biogenesis ◽  
Human Breast Cancer ◽  
Breast Cancer Cells ◽  
Signalling Pathways ◽  
Human Breast Cancer Cells ◽  
Human Breast ◽  
Mcf 7

Abstract Background Although produced by several types of tumours, the role of serotonin on cancer biology is yet to be understood. Methods The effects of serotonin (5-HT) on human breast cancer cells proliferation, signalling pathways and metabolic profile were evaluated by cytometry, western blotting, qPCR, enzymology and confocal microscopy. Results Our results revealed that incubation of MCF-7 cells with 10 µM 5-HT increased cell growth rate by 28%, an effect that was prevented by the 5-HTR2A/C antagonist, ketanserin. Conversely, increasing concentrations of 5-HT promoted glucose consumption and lactate production by MCF-7 cells. We also showed that increased glucose metabolism is provoked by the upregulation of pyruvate kinase M2 (PKM2) isoform through 5-HTR2A/C-triggered activation of Jak1/STAT3 and ERK1/2 subcellular pathways. However, we noticed a decrease in the rate of produced lactate per consumed glucose as a function of the hormone concentration, suggesting a disruption of the Warburg effect. The latter effect is due to 5-HTR2A/C-dependent mitochondrial biogenesis and metabolism, which is triggered by adenylyl cyclase/PKA, enhancing the oxidation of lactate within these cells. Conclusions We showed that serotonin, through 5-HTR2A/C, interferes with breast cancer cells proliferation and metabolism by triggering two distinct signalling pathways: Jak1/STAT3 that boosts glycolysis through upregulation of PKM2, and adenylyl cyclase/PKA that enhances mitochondrial biogenesis.

scholarly journals Oestrogen receptor alpha increases p21(WAF1/CIP1) gene expression and the antiproliferative activity of histone deacetylase inhibitors in human breast cancer cells

2003 ◽  
Vol 179 (1) ◽  
pp. 41-53 ◽  
Author(s):  
R Margueron ◽  
A Licznar ◽  
G Lazennec ◽  
F Vignon ◽  
V Cavailles
Keyword(s):  
Breast Cancer ◽  
Gene Expression ◽  
Cancer Cells ◽  
Histone Deacetylase ◽  
Human Breast Cancer ◽  
Oestrogen Receptor ◽  
Breast Cancer Cells ◽  
Human Breast Cancer Cells ◽  
Human Breast ◽  
P21 Waf1

We analysed the antiproliferative activity of various histone deacetylase (HDAC) inhibitors such as trichostatin A (TSA) on human breast cancer cells. We observed a lower sensitivity to HDAC inhibition for oestrogen receptor negative (ER-) versus positive (ER+) cell lines. This differential response was associated neither with a modification of drug efflux via the multidrug resistance system nor with a global modification of histone acetyltransferase (HAT)/HDAC activities. In contrast, we demonstrated that in ER+ breast cancer cells the p21(WAF1/CIP1) gene was more sensitive to TSA regulation and was expressed at higher levels. These differences were observed both in transient transfection experiments and on the endogenous p21(WAF1/CIP1) gene. The Sp1 transcription factor, which was shown to interact in vitro with both class I and class II HDACs, is sufficient to confer the differential sensitivity to TSA and participated in the control of p21(WAF1/CIP1) basal expression. Finally, re-expression of ERalpha following adenoviral infection of ER- breast cancer cells increased both p21(WAF1/CIP1) protein accumulation and the growth inhibitory activity of TSA. Altogether, our results highlight the key role of ERalpha and p21(WAF1/CIP1) gene expression in the sensitivity of breast cancer cells to hyperacetylating agents.

scholarly journals Cytotoxic Potential of Flavonoid from Nicotiana tabacum Leaves on MCF-7 Human Breast Cancer Cells

2020 ◽  
Vol 11 (2) ◽  
pp. 97
Author(s):  
Banun Kusumawardani ◽  
Qonita Nafilah Febi ◽  
Malihatul Rosidah ◽  
Deri Abdul Azis ◽  
Endah Puspitasari ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cell Viability ◽  
Cancer Cells ◽  
Human Breast Cancer ◽  
Breast Cancer Cells ◽  
Vero Cells ◽  
Human Breast Cancer Cells ◽  
Human Breast ◽  
Tobacco Leaves ◽  
Mcf 7

Flavonoid has potential bioactivity as anticancer agents. The flavonoid of cultivated tobacco (Nicotiana tabacum), locally known as “Kasturi”, leaves was screened for its cytotoxicity against MCF-7 human breast cancer cells and non-transformed Vero cells (African normal cell kidney line) in different concentrations. This study aimed to examine the cytotoxic potential of the flavonoid of Kasturi tobacco leaves against MCF-7 human breast cancer cells. Flavonoid obtained from methanolic extracts of Kasturi tobacco leaves, which have been purified from nicotine. The flavonoid of Kasturi tobacco leaves with concentrations of 20 to 640 μg/mL were exposed to MCF-7 and Vero cells for 24 h. Cell viability was evaluated by 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay. Flavonoid of Kasturi tobacco leaves with concentrations of 160 μg/mL decreased the MCF-7 cell viability more than 50%, with an inhibitory concentration 50 (IC50) value of 148.41 μg/mL. Meanwhile, it inhibited 50% of Vero cell viability at 255.35 μg/mL. The flavonoid of Kasturi tobacco leaves has cytotoxic activity on MCF-7 cells, and might be a potential alternative agent for human breast cancer therapy.Keywords: flavonoid, tobacco leaves, human breast cancer cells, anticancer activity

scholarly journals Therapeutic CK2 inhibition attenuates diverse prosurvival signaling cascades and decreases cell viability in human breast cancer cells

Oncotarget ◽  
2014 ◽  
Vol 5 (15) ◽  
pp. 6484-6496 ◽  
Author(s):  
G. Kenneth Gray ◽  
Braden C. McFarland ◽  
Amber L. Rowse ◽  
Sara A. Gibson ◽  
Etty N. Benveniste
Keyword(s):  
Breast Cancer ◽  
Cell Viability ◽  
Cancer Cells ◽  
Human Breast Cancer ◽  
Breast Cancer Cells ◽  
Signaling Cascades ◽  
Human Breast Cancer Cells ◽  
Human Breast
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