scholarly journals Effects of a phytoestrogen-containing soy extract on the growth-inhibitory activity of ICI 182 780 in an experimental model of estrogen-dependent breast cancer

2007 ◽  
Vol 14 (2) ◽  
pp. 317-324 ◽  
Author(s):  
Daniela Gallo ◽  
Elisabetta Mantuano ◽  
Manuela Fabrizi ◽  
Cristiano Ferlini ◽  
Simona Mozzetti ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Inhibitory Activity ◽  
Concomitant Administration ◽  
Breast Cancer Cell Lines ◽  
Concomitant Treatment ◽  
Drug Induced ◽  
Mrna Gene ◽  
Positive Breast Cancer Cell ◽  
Mcf 7

The study reported here was designed to determine whether a phytoestrogen-containing soy extract (SSE) could negate/overwhelm the inhibitory effects of ICI 182 780 on the growth of estrogen-sustained human breast cancer xenografts (MCF-7), in ovariectomized athymic mice. As expected, estradiol-supplemented tumors did not grow over the study period in ICI 182 780-treated females; concomitant administration of 50 mg/kg per day SSE slightly potentiated the inhibitory activity of the drug, while at 100 mg/kg per day, SSE partially negated ICI 182 780 activity. In keeping with these in vivo outcomes, we observed that the level of cyclin D1 (and progesterone receptor) in MCF-7 xenografts was considerably reduced by ICI 182 780, an effect enhanced by concomitant treatment with 50 SSE, but reduced by the higher dosage (i.e. 100 mg/kg per day). Thrombospondin-1 (TSP-1) and kallikrein 6 (KLK6) levels were also reduced following ICI 182 780, although to a lesser degree; again, combined anti-estrogen and SSE produced a dose-dependent regulation in TSP-1 and KLK6 tumor level, with a further reduction in the mRNA gene expression at 50 SSE (compared with ICI 182 780) and a partial reversion of the drug-induced down-regulation at 100 mg/kg per day. No modulation was detected in the serum concentration of IGF-1 (a potent mitogen for estrogen receptor-positive breast cancer cell lines) either upon treatment with ICI 182 780 or concomitant administration of the anti-estrogen with SSE. In conclusion, results from this study raise concerns about the consumption of isoflavone supplements in conjunction with ICI 182 780 therapy, in postmenopausal women with estrogen-dependent breast cancer.

scholarly journals Cell Context-Dependent Differences in the Induction of E2F-1 Gene Expression by 17β-Estradiol in MCF-7 and ZR-75 Cells

Endocrinology ◽  
2003 ◽  
Vol 144 (5) ◽  
pp. 1675-1685 ◽  
Author(s):  
Sharon Ngwenya ◽  
Stephen Safe
Keyword(s):  
Breast Cancer ◽  
Gene Expression ◽  
Chimeric Protein ◽  
Gene Promoter ◽  
Estrogen Receptor Α ◽  
Breast Cancer Cell Lines ◽  
Er Positive ◽  
17Β Estradiol ◽  
Positive Breast Cancer Cell ◽  
Mcf 7

17β-Estradiol (E2) induces E2F-1 gene expression in ZR-75 and MCF-7 human breast cancer cells. Analysis of the E2F-1 gene promoter in MCF-7 cells previously showed that hormone-induced transactivation required interactions between estrogen receptor α (ERα)/Sp1 bound to upstream GC-rich sites and NFYA bound to downstream CCAAT sites within the −169 to −54 region of the promoter. This same region of the E2F-1 promoter was also E2 responsive in ERα-positive ZR-75 cells; however, further analysis of the promoter showed that cooperative ERα/Sp1/NFY interactions were not necessary for hormone-induced transactivation in ZR-75 cells. The upstream GC-rich motifs (−169 to −111) are activated independently by ERα/Sp1 in ZR-75 but not MCF-7 cells, and a construct (pE2F-1jm1) containing the −122 to −54 downstream CCAAT site that bound NFYA was also E2 responsive. E2 also induced reporter gene activity in ZR-75 cells transfected with an expression plasmid for a chimeric protein containing the DNA-binding domain of the yeast GAL4 protein fused to NFYA (pM-NFYA) and a construct containing five tandem GAL4 response elements. Subsequent studies showed that hormonal activation of pE2F-1jm1 and pM-NFYA are dependent on nongenomic pathways in which E2 activates cAMP/protein kinase A. Hormone-dependent regulation of E2F-1 gene expression in ZR-75 and MCF-7 involves the same cis elements and interacting transcription factors but different mechanisms, demonstrating the importance of cell context on transactivation pathways, even among ER-positive breast cancer cell lines.

scholarly journals Computational, Pharmacological and Toxicological Approach of Repurposed Lamotrigine Schiff Base Derivatives for Reduction of Hormone-Positive Breast Tumor

2021 ◽  
Author(s):  
Saima Najm ◽  
Humaira Naureen ◽  
Fareeha Anwar ◽  
Muhammad Mubbashir Khan ◽  
Rabia Ali
Keyword(s):  
Breast Cancer ◽  
Schiff Base ◽  
Cell Lines ◽  
Cancer Cell ◽  
Breast Cancer Cell ◽  
Cancer Cell Lines ◽  
Breast Cancer Cell Lines ◽  
Mcf 7

Abstract Background and objectives: Breast cancer presents high morbidity among women with various treatment challenges. This study aims to evaluate the repurposed lamotrigine schiff base metal (LTG-SB-M) coordinates against in-vitro MCF-7 breast cancer cell lines and in-vivo N-methylnitrosourea (NMU)-persuaded toxicity of rats’ mammary gland. Method: In-silico computational analysis and in vitro cytotoxic studies on MCF-7 breast cancer cell lines was executed to build up the assumptions. In-vivo NMU-induced anticancer potential was assessed in forty Wistar rats; assigned into five groups of 8 rats each. Group I served as normal control and received normal saline, Group II received NMU (50 mg/kg), Group III received tamoxifen, whereas; Group IV and V received LTG-SB-M derivative (LAC3, LBC3) at dose of 100 mg/kg body weight, for 15 consecutive days. Intraperitoneal injection of NMU (single dose) was given at the age of 5, 9 and 13 weeks to the rats with the three week interval. For all experimental animals; biochemical markers were assessed. DNA strand breakage alongside the hormonal profile of estrogen and progesterone was also estimated. Results: All tested compounds present significant activity against MCF-7 cell lines in vitro and NMU-induced mammary tumor in vivo. The in vivo results of tested compounds present a significant decrease in weight of organ; with reinstated renal and hepatic enzymes. Histological analysis revealed strong countenance of proteins, estrogen, and progesterone in NMU-treated rats. Conclusion: These results suggest that LTG-SB-M complex can be used as better anticancer agent against breast cancer.

The synergistic effect between celecoxib and luteolin and dependence on estrogen receptor in human breast cancer cells.

2015 ◽  
Vol 33 (28_suppl) ◽  
pp. 135-135
Author(s):  
Ye-Won Jeon ◽  
Youngjin Suh
Keyword(s):  
Breast Cancer ◽  
Cancer Cells ◽  
Cell Lines ◽  
Combination Treatment ◽  
Breast Cancer Cells ◽  
Synergistic Effects ◽  
Breast Cancer Cell Lines ◽  
Human Breast ◽  
Mcf 7

135 Background: The anti-cancer effects of celecoxib and luteolin are well known. Although our previous study demonstrated that the combination of celecoxib and luteolin synergistically inhibits breast tumor growth compared with each of the treatments alone, we did not uncover the molecular mechanisms of these effects. The aims of our present study were to compare the effects of a celecoxib and luteolin combination treatment in four different human breast cell lines and to determine the mechanisms of action in vitro and in vivo. Methods: Using MCF-7, MCF7/HER18, MDA-MB-231 and SkBr3 human breast cancer cells, proliferation assay, apoptosis assay, inhibition assay with MEK and PI3K inhibitor in addition to western blotting and xenograft study after treatment with celecoxib and luteolin. Results: The synergistic effects of a celecoxib and luteolin combination treatment yielded significantly greater cell growth inhibition in all four breast cancer cell lines compared with the single agents alone. In particular, combined celecoxib and luteolin treatment significantly decreased the growth of MDA-MB-231 cancer cells in vivo compared with either agent alone. The celecoxib and luteolin combination treatment induced synergistic effects via Akt inactivation and extracellular signal-regulated kinase (ERK) signaling inhibition in MCF-7 and MCF7/HER18 cells and via Akt inactivation and ERK signaling activation in MDA-MB-231 and SkBr3 cells. Conclusions: These results demonstrate the synergistic anti-tumor effect of the celecoxib and luteolin combination treatment in different four breast cancer cell lines, thus introducing the possibility of this combination as a new treatment modality.

scholarly journals One-Step 18F-Labeling of Estradiol Derivative for PET Imaging of Breast Cancer

2018 ◽  
Vol 2018 ◽  
pp. 1-9
Author(s):  
Hongbo Huang ◽  
Ke Li ◽  
Gaochao Lv ◽  
Guiqing Liu ◽  
Xueyu Zhao ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Pet Imaging ◽  
Cell Uptake ◽  
Breast Cancer Cell Lines ◽  
Breast Cancers ◽  
Isotope Exchange Reaction ◽  
Er Positive ◽  
One Step ◽  
Mcf 7

Positron emission tomography (PET) imaging is a useful method to evaluate in situ estrogen receptor (ER) status for the early diagnosis of breast cancer and optimization of the appropriate treatment strategy. The 18F-labeled estradiol derivative has been successfully used to clinically assess the ER level of breast cancer. In order to simplify the radiosynthesis process, one-step 18F-19F isotope exchange reaction was employed for the 18F-fluorination of the tracer of [18F]AmBF3-TEG-ES. The radiotracer was obtained with the radiochemical yield (RCY) of ~61% and the radiochemical purity (RCP) of >98% within 40 min. Cell uptake and blocking assays indicated that the tracer could selectively accumulate in the ER-positive human breast cancer cell lines MCF-7 and T47D. In vivo PET imaging on the MCF-7 tumor-bearing mice showed relatively high tumor uptake (1.4~2.3 %D/g) and tumor/muscle uptake ratio (4~6). These results indicated that the tracer is a promising PET imaging agent for ER-positive breast cancers.

scholarly journals The Potential Utility of Curcumin in the Treatment of HER-2-Overexpressed Breast Cancer: AnIn VitroandIn VivoComparison Study with Herceptin

2012 ◽  
Vol 2012 ◽  
pp. 1-12 ◽  
Author(s):  
Hung-Wen Lai ◽  
Su-Yu Chien ◽  
Shou-Jen Kuo ◽  
Ling-Ming Tseng ◽  
Hui-Yi Lin ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Signal Transduction ◽  
Cell Growth ◽  
Xenograft Model ◽  
Breast Cancer Cell Lines ◽  
Breast Cancers ◽  
Her 2 ◽  
Mcf 7

HER-2 is an important oncoprotein overexpressed in about 15–25% of breast cancers. We hypothesized that the ability of curcumin to downregulate HER-2 oncoprotein and inhibit the signal transduction pathway of PI3K/Akt, MAPK, and NF-κB activation may be important in the treatment of HER-2-overexpressed breast cancer. To examine the effect of curcumin on breast cancer cells, MCF-7, MDA-MB-231, MCF-10A, BT-474, and SK-BR-3-hr (a herceptin resistant strain from SK-BR-3) cells were used forin vitroanalysis. Thein vivoeffect of curcumin on HER-2-overexpressed breast cancer was investigated with the HER-2-overexpressed BT-474 xenograft model. Cell growth, cell cycle change, the antimobility effect, signal transduction, and xenograft volume analysis between groups treated with herceptin and/or curcumin were tested. Curcumin decreased the cell growth of various breast cancer cell lines (MCF-7, MDA-MB-231, MCF-10A, BT-474, and SK-BR-3-hr). In Western blot analysis, the phosphorylation of Akt, MAPK, and expression of NF-κB were reduced in BT-474 cells, but not in SK-BR-3-hr cells, after treatment with herceptin. When treated with curcumin, the HER-2 oncoprotein, phosphorylation of Akt, MAPK and expression of NF-κB were decreased in both BT-474 and SK-BR-3-hr cells. In the BT-474 xenograft model, though not as much as herceptin, curcumin did effectively decrease the tumor size. The combination of curcumin with herceptin was not better than herceptin alone; however, the combination of taxol and curcumin had an antitumor effect comparable with taxol and herceptin. The results suggested that curcumin has potential as a treatment for HER-2-overexpressed breast cancer.

scholarly journals Jujuboside B Inhibits the Proliferation of Breast Cancer Cell Lines by Inducing Apoptosis and Autophagy

2021 ◽  
Vol 12 ◽  
Author(s):  
Lin Guo ◽  
Yupei Liang ◽  
Shiwen Wang ◽  
Lihui Li ◽  
Lili Cai ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cell Lines ◽  
Cancer Cell ◽  
Breast Cancer Cell ◽  
Cancer Cell Lines ◽  
Biologically Active ◽  
Breast Cancer Cell Lines ◽  
Induced Apoptosis ◽  
Mcf 7

Jujuboside B (JB) is one of the main biologically active ingredients extracted from Zizyphi Spinosi Semen (ZSS), a widely used traditional Chinese medicine for treating insomnia and anxiety. Breast cancer is the most common cancer and the second leading cause of cancer-related death in women worldwide. The purpose of this study was to examine whether JB could prevent breast cancer and its underlying mechanism. First, we reported that JB induced apoptosis and autophagy in MDA-MB-231 and MCF-7 human breast cancer cell lines. Further mechanistic studies have revealed that JB-induced apoptosis was mediated by NOXA in both two cell lines. Moreover, the AMPK signaling pathway plays an important role in JB-induced autophagy in MCF-7. To confirm the anti-breast cancer effect of JB, the interaction of JB-induced apoptosis and autophagy was investigated by both pharmacological and genetic approaches. Results indicated that autophagy played a pro-survival role in attenuating apoptosis. Further in vivo study showed that JB significantly suppressed the growth of MDA-MB-231 and MCF-7 xenografts. In conclusion, our findings indicate that JB exerts its anti-breast cancer effect in association with the induction of apoptosis and autophagy.

Anti-estrogenic effect of TAS-108 in breast cancer cell lines.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. e11029-e11029
Author(s):  
Hadong Kim ◽  
Young Choi ◽  
Tae-Hoon Kim
Keyword(s):  
Breast Cancer ◽  
Epithelial Cells ◽  
Growth Inhibition ◽  
Cell Lines ◽  
Cancer Cell ◽  
Breast Cancer Cell ◽  
Breast Cancer Cell Lines ◽  
Luminal Epithelial Cells ◽  
Mcf 7

e11029 Background: TAS-108 (TAS) is an antiestrogen that binds to both ERα and ERβ and inhibits both estrogen-dependent and independent tumors and TAM resistant tumors. Breast cancer cell lines (BCC) with different pheno- and genotypes are reasonably acceptable models of in vivo breast cancer cell behavior. Thus, we have investigated anti-estrogenic activity of TAS on BCC in the presence of diarylpropionitrile (DPN), a pure ERβ agonist to find ERβ role in TAS activity. Methods: Cultured cells of (1) MCF-7 and ZR-75 (luminal epithelial cells), (2) BT-474 and SK-BR-3 (weakly luminal epithelial cells), and (3) MDA-MB-231 and Hs578T (invasive, mesenchymal-like cells) were treated with: (1) increasing concentrations of DPN or E2, (2) 100nM of 4-hydroxytamoxifen (4-HT) or TAS, and (3) 100nM of DPN or E2 with increasing concentrations of either 4-HT or TAS. After 6 days, cell proliferation was analyzed. The mRNA levels of ERβ and ERα isoform were determined by RT-qPCR. ERα, PR, and Her-2 status was determined by IHC. Percent proliferation compared to the control was calculated and P <0.05 based on T-test was considered significant. Results: The most significant proliferation and growth inhibition was seen in MCF-7 BCC. In the presence of DPN, IC50 (50% inhibitory concentration) was 12.5nmol of TAS vs 33.1nmol of 4-HT. In the presence of E2, IC50 was 2.15 nmol of TAS vs 49.7nmol of 4-HT. Other BCC showed insignificant or variable proliferative and inhibitory response. Overall, DPN displayed high proliferation in most BCC. TAS exhibited higher growth inhibition than 4-HT. Conclusions: Variable responses of different BCC lines to ERα and ERβ agonists and antagonists may be instructive in modeling in vivo breast cancer response to these compounds. Overall, exposure to ERβ agonists showed a significant proliferation in ERα+, ERα- and ERβ+ cells. TAS activity was more pronounced and its anti-estrogen activity may involve ERβ in addition to ERα. [Table: see text]

scholarly journals The effects and possible mechanism of action of apolipoprotein M on the growth of breast cancer cells

2021 ◽  
Author(s):  
Ying Zhou ◽  
Shuang Yao ◽  
Miaomei Yu ◽  
Jiang Wei ◽  
Qi Fang ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Mechanism Of Action ◽  
Breast Cancer Cells ◽  
Animal Experiments ◽  
Breast Cancer Cell Lines ◽  
Apolipoprotein M ◽  
Main Pathway ◽  
The Difference ◽  
Mcf 7

Abstract Background: To investigate the effects and mechanism of action of apolipoprotein M (ApoM) on the growth of breast cancer (BC) cells.Methods and Results: Bioinformatics, cell experiments and animal experiments were used to verify the effect of ApoM on breast cancer cell lines and breast tumor growth in vivo. ApoM expression was significantly reduced in BC tissues, and patients with lower ApoM mRNA expression had a poorer prognosis (P<0.0001). Besides, ApoM can partially inhibit the proliferative, migratory and invasive processes of BC cells. In vivo, the difference between ApoM-OE and NC groups was no significant. The level of vitamin D receptor (VDR) protein in MDA-MB-231 cells was increased by overexpression of ApoM (P<0.05), while in MCF-7 cells, VDR levels decreased (P<0.05).Conclusions: ApoM can partially inhibit the growth of BC cells. VDR may play a role, but is not the main pathway.

scholarly journals miR-200c suppresses stemness and increases cellular sensitivity to trastuzumab in HER2+ breast cancer

2017 ◽  
Author(s):  
Cailu Song ◽  
Jin Wang ◽  
Hua Wang ◽  
Peng Liu ◽  
Longzhong Liu ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Stem Cells ◽  
Target Genes ◽  
Breast Cancer Cell Lines ◽  
Breast Cancer Patients ◽  
Trastuzumab Resistance ◽  
Her2 Positive ◽  
Her2 Breast Cancer ◽  
Mcf 7

AbstractResistance to trastuzumab remains a major obstacle in HER2-overexpressing breast cancer treatment. miR-200c is important for many functions in cancer stem cells (CSCs), including tumor recurrence, metastasis and resistance. We hypothesized that miR-200c contributes to trastuzumab resistance and stemness maintenance in HER2-overexpressing breast cancer. In this study, we used HER2-positive SKBR3, HER2-negative MCF-7, and their CD44+CD24- phenotype mammospheres SKBR3-S and MCF-7-S to verify. Our results demonstrated that miR-200c was weakly expressed in breast cancer cell lines and cell line stem cells. Overexpression of miR-200c resulted in a significant reduction in the number of tumor spheres formed and the population of CD44+CD24- phenotype mammospheres in SKBR3-S. Combining miR-200c with trastuzumab can significantly reduce proliferation and increase apoptosis of SKBR3 and SKBR3-S. Overexpression of miR-200c also eliminated its downstream target genes. These genes were highly expressed and positively related in breast cancer patients. Overexpression of miR-200c also improved the malignant progression of SKBR3-S and SKBR3 in vivo. miR-200c plays an important role in the maintenance of the CSC-like phenotype and increases drug sensitivity to trastuzumab in HER2+ cells and stem cells.Summary statementmiRNAs are critical in stemness maintenance and drug resistance. These data link maintenance of the stemness-related phenotype and the sensitivity of HER2+ breast cancer to miR-200c in response to trastuzumab.

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