scholarly journals Overexpression of wild-type p53 gene renders MCF-7 breast cancer cells more sensitive to the antiproliferative effect of progesterone

2003 ◽  
Vol 179 (1) ◽  
pp. 55-62 ◽  
Author(s):  
M Alkhalaf ◽  
AM El-Mowafy
Keyword(s):  
Breast Cancer ◽  
Cell Growth ◽  
Growth Inhibition ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
P53 Protein ◽  
P53 Gene ◽  
Inhibitory Effect ◽  
Antiproliferative Effect ◽  
Mcf 7

We have recently shown that growth inhibition of breast cancer cells by progesterone is due to the induction of cell differentiation, but not apoptosis. Because the tumor suppressor protein p53 plays a central role in normal cell growth and in tumor suppression, we have examined the effect of progesterone on the levels of this protein in MCF-7 cells. We show here that the antiproliferative effect of progesterone is accompanied with down-regulation of endogenous p53 protein. To study the effect of progesterone on cell growth in the presence of normal levels of p53 protein, we used transient transfection to overexpress p53 protein. MCF-7 cells were transfected with a p53 expressing vector that contains p53 human cDNA under the control of a cytomegalovirus promoter. Cell growth, cell viability, and apoptosis were analyzed in the transfected cells after six days of exposure to 100 nM progesterone. We show here that progesterone significantly enhances growth inhibition and apoptosis in MCF-7 cells overexpressing p53, but not in cells transfected with the control vector. These data suggest that re-establishing p53 function in MCF-7 breast cancer cells renders them more sensitive to the growth inhibitory effect of progesterone.

Abstract P005: GRK4 Inhibitors Suppress Breast Cancer Cell Growth And Potentiate The Inhibitory Effect Of Dopaminergic D 1 Receptor Agonist SKF38393

Hypertension ◽  
2020 ◽  
Vol 76 (Suppl_1) ◽  
Author(s):  
Wei Yue ◽  
Jiping Wang ◽  
John J Gildea ◽  
Peng Xu ◽  
Stephen Marshall ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Growth Inhibition ◽  
Cancer Cells ◽  
Sodium Excretion ◽  
Breast Cancer Cells ◽  
Inhibitory Effect ◽  
Cell Number ◽  
Compound A ◽  
Compound C ◽  
Mcf 7

The renal dopaminergic D 1 receptor (D 1 R) regulates sodium excretion which is terminated by phosphorylation by G protein-coupled receptor kinases 4 (GRK4). GRK4 gene variants are associated with increased GRK4 activity and reduced sodium excretion resulting in hypertension. Breast cancer incidence is higher in hypertensive women. We found that GRK4 is a potential molecule linking these two diseases. We hypothesized that GRK4 inhibitors would be beneficial to patients with hypertension and breast cancer. Three potential GRK4 inhibitors (compounds A, B, and C) were tested for their effect on the growth of breast cancer cells MDA-MB-468, MCF-7, and benign mammary epithelial cells MCF-10A controls. These cell lines had high, low, and no GRK4 expression respectively. Growth of MDA-MB-468 and MCF-7 cells was effectively inhibited by compound C with IC 50 16.8±1.9 nM (n=2). MCF-10A cells were relatively resistant to compound C with IC 50 49.3±4.0 nM (n=3) that is significantly higher than the cancer cells (p<0.001). Compound B was the least effective inhibitor in all three cell lines (IC 50 was 1.5-2.3 μM). Growth inhibition of compound A was similar in MCF-7 and MCF-10A cells but less effective in MDA-MB-468 cells indicating GRK4 inhibition may not be the only target for growth inhibition of this compound. It has been reported that D 1 R agonists inhibit growth of breast cancer cells. We hypothesized that blockade of GRK4 would increase sensitivity of breast cancer cells to the inhibitory effect of a D 1 R agonist. In MDA-MB-468 cells, SKF38393 (SKF) at 20 μM caused a 36% reduction in cell number (from 276.7±0.47E4 to 177.7±4.33E4). Compound C alone reduced cell number by 37% (172.4±0.04E4, 5 nM) and 51% (136.3±7.87E4, 10 nM) respectively. Combination treatment induced more reduction in cell number, 63% (100.4±5.54E4, 5 nM) and 84% (44.1±12.7E4, 10 nM). Similarly, Compound A also enhanced the inhibitory effect of SKF. A left-shift of the SKF dose-response curve in GKR4 knock-down MDA-MB-468 cells confirmed that inhibition of GRK4 increases sensitivity of breast cancer cells to SKF. Our preliminary results suggest that targeting GRK4 with compound C and a dopaminergic agonist could be a novel strategy for breast cancer therapy especially for the patients with hypertension.

scholarly journals Resveratrol Regulates Insulin-Like Growth Factor-II in Breast Cancer Cells

Endocrinology ◽  
2005 ◽  
Vol 146 (10) ◽  
pp. 4224-4233 ◽  
Author(s):  
Sharda Vyas ◽  
Yayesh Asmerom ◽  
Daisy D. De León
Keyword(s):  
Breast Cancer ◽  
Cell Growth ◽  
Cancer Cells ◽  
Hormonal Regulation ◽  
Breast Cancer Cells ◽  
Inhibitory Effect ◽  
T47d Cells ◽  
Igf I ◽  
17Β Estradiol ◽  
Mcf 7

IGF-II is a potent mitogen and inhibitor of apoptosis in breast cancer. Regulation of IGF-II is complex and includes inhibition by tumor suppressors, stimulation by oncogenes, and imprinting and hormonal regulation by estrogens. Resveratrol (RSV) is a phytoestrogen that displays estrogen-like agonistic and antagonistic activity. Recent studies have shown that RSV inhibits the growth of breast cancer cells and may represent a potent agent in chemopreventive therapy. Because 17β-estradiol regulates IGF-II, we hypothesized that RSV may have a similar effect on IGF-II. The present study was designed to examine whether: 1) RSV modulates IGF-II in breast cancer cells; 2) regulation of IGF-II by RSV is dependent on the ER status; and 3) IGF-II (not IGF-I) mediates RSV effects on breast cancer cells. Treatment of MCF-7 and T47D cells with RSV (10−6m) caused stimulation of precursor IGF-II mRNA and protein; this effect was blocked by coincubation with 17β-estradiol (10−9m). Cell growth stimulated by RSV (10−6m) was blocked by addition of a blocking IGF-I receptor antibody, or the antiestrogen tamoxifen (10−7m). In contrast, RSV treatment (10−4m) inhibited IGF-II secretion and cell growth in MCF-7 and T47D cells. No increase in IGF-II levels is seen in estrogen receptor (−) MCF-10 cells, even though cell growth was inhibited by RSV 10−4m and precursor IGF-II blocked the inhibitory effect of resveratrol. No change in IGF-I was observed with RSV treatment (10−6 to 10−4m). Our study demonstrates that RSV regulates IGF-II and that IGF-II mediates RSV effect on cell survival and growth in breast cancer cells.

scholarly journals Characterising the Response of Human Breast Cancer Cells to Polyamine Modulation

Biomolecules ◽  
2021 ◽  
Vol 11 (5) ◽  
pp. 743
Author(s):  
Oluwaseun Akinyele ◽  
Heather M. Wallace
Keyword(s):  
Breast Cancer ◽  
Cell Proliferation ◽  
Cell Growth ◽  
Cancer Cells ◽  
Cell Lines ◽  
Cancer Cell ◽  
Breast Cancer Cells ◽  
Growth Responses ◽  
Cancer Management ◽  
Mcf 7

Breast cancer is a complex heterogeneous disease with multiple underlying causes. The polyamines putrescine, spermidine, and spermine are polycationic molecules essential for cell proliferation. Their biosynthesis is upregulated in breast cancer and they contribute to disease progression. While elevated polyamines are linked to breast cancer cell proliferation, there is little evidence to suggest breast cancer cells of different hormone receptor status are equally dependent on polyamines. In this study, we characterized the responses of two breast cancer cells, ER+ (oestrogen receptor positive) MCF-7 and ER- MDA-MB-231 cell lines, to polyamine modulation and determined the requirement of each polyamine for cancer cell growth. The cells were exposed to DFMO (a polyamine pathway inhibitor) at various concentrations under different conditions, after which several growth parameters were determined. Exposure of both cell lines to DFMO induced differential growth responses, MCF-7 cells showed greater sensitivity to polyamine pathway inhibition at various DFMO concentrations than the MDA-MB-231 cells. Analysis of intracellular DFMO after withdrawal from growth medium showed residual DFMO in the cells with concomitant decreases in polyamine content, ODC protein level, and cell growth. Addition of exogenous polyamines reversed the cell growth inhibition, and this growth recovery appears to be partly dependent on the spermidine content of the cell. Similarly, DFMO exposure inhibits the global translation state of the cells, with spermidine addition reversing the inhibition of translation in the breast cancer cells. Taken together, these data suggest that breast cancer cells are differentially sensitive to the antitumour effects of polyamine depletion, thus, targeting polyamine metabolism might be therapeutically beneficial in breast cancer management based on their subtype.

scholarly journals Sphingosine Kinase Transmits Estrogen Signaling in Human Breast Cancer Cells

2003 ◽  
Vol 17 (10) ◽  
pp. 2002-2012 ◽  
Author(s):  
Olga A. Sukocheva ◽  
Lijun Wang ◽  
Nathaniel Albanese ◽  
Stuart M. Pitson ◽  
Mathew A. Vadas ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cell Growth ◽  
Cancer Cells ◽  
Human Breast Cancer ◽  
Breast Cancer Cells ◽  
Sphingosine Kinase ◽  
Human Breast Cancer Cells ◽  
Human Breast ◽  
Mcf 7 ◽  
Cytoplasmic Signaling

Abstract Current understanding of cytoplasmic signaling pathways that mediate estrogen action in human breast cancer is incomplete. Here we report that treatment with 17β-estradiol (E2) activates a novel signaling pathway via activation of sphingosine kinase (SphK) in MCF-7 breast cancer cells. We found that E2 has dual actions to stimulate SphK activity, i.e. a rapid and transient activation mediated by putative membrane G protein-coupled estrogen receptors (ER) and a delayed but prolonged activation relying on the transcriptional activity of ER. The E2-induced SphK activity consequently activates downstream signal cascades including intracellular Ca2+ mobilization and Erk1/2 activation. Enforced expression of human SphK type 1 gene in MCF-7 cells resulted in increases in SphK activity and cell growth. Moreover, the E2-dependent mitogenesis were highly promoted by SphK overexpression as determined by colony growth in soft agar and solid focus formation. In contrast, expression of SphKG82D, a dominant-negative mutant SphK, profoundly inhibited the E2-mediated Ca2+ mobilization, Erk1/2 activity and neoplastic cell growth. Thus, our data suggest that SphK activation is an important cytoplasmic signaling to transduce estrogen-dependent mitogenic and carcinogenic action in human breast cancer cells.

VITAMIN D DERIVATIVES IN COMBINATION WITH 9-cis RETINOIC ACID PROMOTE ACTIVE CELL DEATH IN BREAST CANCER CELLS

1995 ◽  
Vol 14 (3) ◽  
pp. 391-394 ◽  
Author(s):  
S Y James ◽  
A G Mackay ◽  
K W Colston
Keyword(s):  
Breast Cancer ◽  
Vitamin D ◽  
Retinoic Acid ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
P53 Protein ◽  
Protein A ◽  
Therapeutic Implications ◽  
Protein Levels ◽  
Mcf 7

ABSTRACT The effects of the novel vitamin D analogue, EB1089 alone, or in combination with the retinoid, 9-cis retinoic acid (9-cis RA) on indices of apoptosis in MCF-7 breast cancer cells have been examined. EB1089 was capable of reducing bcl-2 protein, a suppressor of apoptosis, and increasing p53 protein levels in MCF-7 cell cultures following 96h treatment. In the presence of 9-cis RA, EB1089 acted to further enhance the down-regulation and up-regulation of bcl-2 and p53 respectively. Furthermore, EB1089 induces DNA fragmentation in MCF-7 cells, a key feature of apoptosis, alone and in combination with 9-cis RA in situ. The observation that EB1089 and 9-cis RA act in a cooperative manner to enhance induction of apoptosis in these cells may have therapeutic implications.

Obtusifoliol related steroids from Euphorbia sogdiana with cell growth inhibitory activity and apoptotic effects on breast cancer cells (MCF-7 and MDA-MB231)

Steroids ◽  
2016 ◽  
Vol 115 ◽  
pp. 90-97 ◽  
Author(s):  
Mahmoud Aghaei ◽  
Zeinab Yazdiniapour ◽  
Mustafa Ghanadian ◽  
Behzad Zolfaghari ◽  
Virginia Lanzotti ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cell Growth ◽  
Cancer Cells ◽  
Inhibitory Activity ◽  
Breast Cancer Cells ◽  
Growth Inhibitory ◽  
Growth Inhibitory Activity ◽  
Apoptotic Effects ◽  
Mcf 7

Growth inhibition, G1-arrest, and apoptosis in MCF-7 human breast cancer cells by novel highly lipophilic 5-fluorouracil derivatives

2004 ◽  
Vol 22 (4) ◽  
pp. 379-389 ◽  
Author(s):  
Juan Antonio Marchal ◽  
Houria Boulaiz ◽  
Inés Suárez ◽  
Estrella Saniger ◽  
Joaquín Campos ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Growth Inhibition ◽  
Cancer Cells ◽  
Human Breast Cancer ◽  
Breast Cancer Cells ◽  
G1 Arrest ◽  
Human Breast Cancer Cells ◽  
Human Breast ◽  
Mcf 7

scholarly journals G Protein-Coupled Receptor 30 Is Critical for a Progestin-Induced Growth Inhibition in MCF-7 Breast Cancer Cells

Endocrinology ◽  
2002 ◽  
Vol 143 (9) ◽  
pp. 3376-3384 ◽  
Author(s):  
Tytti M. Ahola ◽  
Tommi Manninen ◽  
Niina Alkio ◽  
Timo Ylikomi
Keyword(s):  
Breast Cancer ◽  
Growth Inhibition ◽  
Cancer Cells ◽  
G Protein ◽  
Breast Cancer Cells ◽  
G Protein Coupled Receptor ◽  
G Protein Coupled ◽  
Mcf 7

scholarly journals Studies on Multifunctional Effect of All-Trans Retinoic Acid (ATRA) on Matrix Metalloproteinase-2 (MMP-2) and Its Regulatory Molecules in Human Breast Cancer Cells (MCF-7)

2009 ◽  
Vol 2009 ◽  
pp. 1-13 ◽  
Author(s):  
Anindita Dutta ◽  
Triparna Sen ◽  
Aniruddha Banerji ◽  
Shamik Das ◽  
Amitava Chatterjee
Keyword(s):  
Breast Cancer ◽  
Cancer Cells ◽  
Human Breast Cancer ◽  
Breast Cancer Cells ◽  
Gelatin Zymography ◽  
Inhibitory Effect ◽  
Human Breast Cancer Cells ◽  
Human Breast ◽  
Atra Treatment ◽  
Mcf 7

Background. Vitamin A derivative all-trans retinoic acid (ATRA) is considered as a potent chemotherapeutic drug for its capability of regulating cell growth and differentiation. We studied the effect of ATRA on MMP-2 in MCF-7, human breast cancer cells, and the probable signaling pathways which are affected by ATRA on regulating pro-MMP-2 activity and expression.Methods. Gelatin zymography, RT-PCR, ELISA, Western blot, Immunoprecipitation, and Cell adhesion assay are used.Results. Gelatin zymography showed that ATRA caused a dose-dependent inhibition of pro-MMP-2 activity. ATRA treatment downregulates the expression of MT1-MMP, EMMPRIN, FAK, NF-kB, and p-ERK. However, expression of E-cadherin, RAR, and CRABP increased upon ATRA treatment. Binding of cells to extra cellular matrix (ECM) protein fibronectin reduced significantly after ATRA treatment.Conclusions. The experimental findings clearly showed the inhibition of MMP-2 activity upon ATRA treatment. This inhibitory effect of ATRA on MMP-2 activity in human breast cancer cells (MCF-7) may result due to its inhibitory effect on MT1-MMP, EMMPRIN, and upregulation of TIMP-2. This study is focused on the effect of ATRA on MMP, MMP-integrin-E-cadherin interrelationship, and also the effect of the drug on different signaling molecules which may involve in the progression of malignant tumor development.

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