Combination of fulvestrant and lapatinib in non-HER2-overexpressing and adriamycin-resistant breast cancer cell lines

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 14050-14050 ◽  
Author(s):  
A. M. Emde ◽  
K. Maslak ◽  
H. Liu ◽  
A. E. Reles ◽  
K. Possinger ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Western Blot ◽  
Cell Lines ◽  
Cancer Cell ◽  
Breast Cancer Cell ◽  
Mtt Assay ◽  
Blot Analysis ◽  
Cancer Cell Lines ◽  
Breast Cancer Cell Lines ◽  
Mcf7 Cells

14050 Background: We evaluated whether combination of lapatinib, a dual tyrosine kinase inhibitor against EGFR and HER2, and fulvestrant, a full estrogen receptor antagonist, is superior in EGFR and HER2 overexpressing and non-overexpressing breast cancer cell lines regarding cell growth inhibition and effects on the protein expression level on special proteins such as PDK1 and ERK1/2. Methods: MTT assay and western blot analysis were performed in the different breast cancer cell lines BT474, T47D, MCF-7 and Adriamycin resistant MCF7 cells. Incubation time was 72h. Concentration of both agents in western blot: 1x10exp-7M, in MTT assay 10exp-11M to 10exp-5M. Results: MTT assay showed a significant stronger proliferation inhibition by lapatinib and fulvestrant in BT474 cells and non- overexpressing T47D cells at a concentration of 10E-7M compared to single agent treatment. By western blot analysis, we found a synergistic downregulation of PDK1 in the combination treatment both in BT474 and AR MCF7 cells, whereas not in T47D cells. In MCF7 cells a downregulation of p-PDK1 was observed after treatment with fulvestrant alone as well as lapatinib plus fulvestrant. Regarding ERK1/2, a synergistic downregulation could be observed in AR MCF7 cells. A downregulation of a p-ERK was detected in MCF-7 cells after treatment with lapatinib, fulvestrant or both. Conclusion: A synergistic action of lapatinib and fulvestrant was observed in all 4 cell lines despite their different receptor status regarding EGFR, HER2 and ER alpha. Shadeo et al. (2005) showed different copy number profiles in these breast cancer cell lines regarding the examined pathways. We could show by western blot analysis that the combination treatment had inhibitory effect on these cell lines according to their individual up-regulated pathways. Altogether, this suggests that the combination is a promising treatment not only in EGFR and HER2 over-expressing breast cancer and that treatment effect is also dependent on up-regulated pathways more likely than receptor status. No significant financial relationships to disclose.

MTT assay dataset of polyethylenimine coated graphenoxide nanosheets on breast cancer cell lines (MCF7, MDA-MB-231, MDA-MB-468)

2020 ◽  
Vol 28 (3) ◽  
pp. 197-202
Author(s):  
Parichehr Maleki ◽  
Zahra Sadeghi ◽  
Sayyed Shahryar Rahpeyma ◽  
Mohammad Taheri ◽  
Jamshid Raheb
Keyword(s):  
Breast Cancer ◽  
Cell Lines ◽  
Cancer Cell ◽  
Breast Cancer Cell ◽  
Mtt Assay ◽  
High Surface ◽  
High Surface Area ◽  
Cancer Cell Lines ◽  
Breast Cancer Cell Lines ◽  
Promising Tool

Graphen oxide has emerged as a promising tool in medical biotechnology due to its outstanding properties applicable in several fields as well as cell imaging, drug and gene delivery. Monolayer structure and high surface area of Graphen benefits elevated loading capacity of drugs rather than other nanomaterials. However Graphen oxide in physiological solutions has unfavourable reactions which confine it’s application in biomedical field without additional surface functionalization. Coating of graphenoxide by polyethylenimine is an approach to enhance biocompatibility of graphen oxide and also provides desirable physicochemical features for oligonucleotides delivery. The data presented here is related to graphenoxide-PEI characterisation and it’s cytotoxicity assay on variouse breast cancer cell lines including MDA-MB-468 and MDA-MB-231 and MCF7 by MTT assay.

scholarly journals PGRMC1 Inhibits Progesterone-Evoked Proliferation and Ca2+ Entry Via STIM2 in MDA-MB-231 Cells

2020 ◽  
Vol 21 (20) ◽  
pp. 7641
Author(s):  
Carlos Cantonero ◽  
Ginés M. Salido ◽  
Juan A. Rosado ◽  
Pedro C. Redondo
Keyword(s):  
Breast Cancer ◽  
Cell Lines ◽  
Cancer Cell ◽  
Breast Cancer Cell ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Cancer Cell Lines ◽  
Nuclear Accumulation ◽  
Breast Cancer Cell Lines ◽  
Mcf7 Cells

Progesterone receptor membrane component 1 (PGRMC1) has been shown to regulate some cancer hallmarks. Progesterone (P4) evokes intracellular calcium (Ca2+) changes in the triple-negative breast cancer cell lines (MDA-MB-231, MDA-MB-468, and BT-20) and in other breast cancer cell lines like the luminal MCF7 cells. PGRMC1 expression is elevated in MDA-MB-231 and MCF7 cells as compared to non-tumoral MCF10A cell line, and PGRMC1 silencing enhances P4-evoked Ca2+ mobilization. Here, we found a new P4-dependent Ca2+ mobilization pathway in MDA-MB-231 cells and other triple-negative breast cancer cells, as well as in MCF7 cells that involved Stromal interaction molecule 2 (STIM2), Calcium release-activated calcium channel protein 1 (Orai1), and Transient Receptor Potential Channel 1 (TRPC1). Stromal interaction molecule 1 (STIM1) was not involved in this novel Ca2+ pathway, as evidenced by using siRNA STIM1. PGRMC1 silencing reduced the negative effect of P4 on cell proliferation and cell death in MDA-MB-231 cells. In line with the latter observation, Nuclear Factor of Activated T-Cells 1 (NFAT1) nuclear accumulation due to P4 incubation for 48 h was enhanced in cells transfected with the small hairpin siRNA against PGRMC1 (shPGRMC1). These results provide evidence for a novel P4-evoked Ca2+ entry pathway that is downregulated by PGRMC1.

scholarly journals Synthesis, Characterization, in silico and in vitro Evaluations of Symmetrical 1,3-Diketones

2020 ◽  
Vol 32 (4) ◽  
pp. 853-864
Author(s):  
V. Porchezhiyan ◽  
D. Kalaivani ◽  
J. Shobana ◽  
S.E. Noorjahan
Keyword(s):  
Breast Cancer ◽  
Binding Affinity ◽  
Cell Lines ◽  
Cancer Cell ◽  
Breast Cancer Cell ◽  
Mtt Assay ◽  
In Silico ◽  
Cancer Cell Lines ◽  
Breast Cancer Cell Lines

1,3-Dicarbonyl compounds have gained significant importance since they are abundantly available in the natural products and possess myriad biological activities. The new symmetrical 1,3-diketones bearing L-proline, 2-methyl-5-iodobenzoic acid, piperidine-3-carboxylic acid and naphthalene-1-acetic acid moieties were synthesized by coupling reaction of appropriate ketone with N-acyl triazole in the presence of MgBr2·Et2O and DIPEA. The chemical structure of the compounds were confirmed from the spectral data such as 1H, 13C NMR, FT-IR and HRMS. Molecular docking studies were carried out for all the compounds with tumor associated protein tyrosine kinase-6 (PTK6) and inflammatory protein cyclooxygenase-2 (COX2). The in vitro evaluation was carried out using breast cancer cell lines (MTT assay) and HRBC stabilization assays. During in silico studies, the ki values obtained against PTK6 and COX2 for (5a-d) compounds were in the range (-7.5 to -10.6) and (-7.6 to -9.8) kcal/mol, respectively. The compound 5d was selected for MTT assay, since it exhibited the highest binding affinity (-10.6 kcal/mol) against PTK6 and gave IC50 - 2.4 μg/mL against breast cancer cell lines. The HRBC stabilization of all the compounds (5a-5d) were in the range (59.28-93.4) %, with highest stabilization value by 5d, which also displayed higher binding affinity with -7.6 kcal/mol towards COX2. Thus, the synthesized symmetrical 1,3-diketones with suitable functionality can be both anticancer and anti-inflammatory agents.

scholarly journals Antiproliferative Effects of Recombinant Apoptin on Lung and Breast Cancer Cell Lines

2020 ◽  
Vol 23 (9) ◽  
pp. 593-599
Author(s):  
Masoud Ezami Razliqi ◽  
Gholamreaza Olad ◽  
Rouhollah Dorostkar ◽  
Sahar Heydari ◽  
Hadi Esmaeili Gouvarchin Ghaleh
Keyword(s):  
Breast Cancer ◽  
Lung Cancer ◽  
Cell Line ◽  
Cell Lines ◽  
Cancer Cell ◽  
Breast Cancer Cell ◽  
Mtt Assay ◽  
Cancer Cell Lines ◽  
Breast Cancer Cell Lines ◽  
Antiproliferative Effects

Background: Selective therapy has always been the main challenge in cancer treatments. Various non-replicative oncolytic viral systems have revealed the safety and efficacy of using viruses and these products. The aim of this paper is to examine the impact of recombinant apoptin on the proliferation of lung cancer and breast cancer cell lines. Methods: The present study consisted of two steps of expression of recombinant apoptin and its anti-proliferative effects on normal and cancer cells. In the first step, following bioinformatics and optimizing apoptin gene sequencing and synthesis, it was expressed using vector PET28a and E. coli BL21 (DE3). The expressed recombinant apoptin was confirmed by analytical SDSPAGE and then purified using Ni affinity chromatography. In the second step, the antiproliferative effects of recombinant apoptin on lung cancer, breast cancer and primary cell lines were determined using MTT assay. Results: According to the results of SDS-PAGE gel assay, recombinant apoptin was visible in the 14 kDa band. Also, the MTT assay results indicated that the antiproliferative effects of recombinant apoptin in cancer cell lines was different compared with the primary cell line, and followed a dose-dependent manner in both cell lines. The highest cytotoxicity (lowest cell viability) groups were 0.2 mg/mL in lung cancer (0.32 ± 0.015) (P<0.001), and in breast cancer (0.33 ± 0.031) (P<0.001) and 0.032 mg/mL in primary cells (0.17 ± 0.004) (P<0.01), as compared to the control groups. Conclusion: Our results confirmed that recombinant apoptin can induce antiproliferative effects in lung cancer and breast cancer cell lines, but not in normal monkey kidney cell line Vero; thus, it can be introduced as a promising novel specific antitumor agent after further evaluation in clinical trials.

scholarly journals Chemically Induced Hypoxia Enhances miRNA Functions in Breast Cancer

Cancers ◽  
2020 ◽  
Vol 12 (8) ◽  
pp. 2008 ◽  
Author(s):  
Emma Gervin ◽  
Bonita Shin ◽  
Reid Opperman ◽  
Mackenzie Cullen ◽  
Riley Feser ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cell Lines ◽  
Cancer Cell ◽  
Breast Cancer Cell ◽  
Metastatic Breast ◽  
Breast Tumors ◽  
Cancer Cell Lines ◽  
Breast Cancer Cell Lines ◽  
Mcf7 Cells ◽  
Cox 2

In aggressively growing tumors, hypoxia induces HIF-1α expression promoting angiogenesis. Previously, we have shown that overexpression of oncogenic microRNAs (miRNAs, miRs) miR526b/miR655 in poorly metastatic breast cancer cell lines promotes aggressive cancer phenotypes in vitro and in vivo. Additionally, miR526b/miR655 expression is significantly higher in human breast tumors, and high miR526b/miR655 expression is associated with poor prognosis. However, the roles of miR526b/miR655 in hypoxia are unknown. To test the relationship between miR526b/miR655 and hypoxia, we used various in vitro, in silico, and in situ assays. In normoxia, miRNA-high aggressive breast cancer cell lines show higher HIF-1α expression than miRNA-low poorly metastatic breast cancer cell lines. To test direct involvement of miR526b/miR655 in hypoxia, we analyzed miRNA-high cell lines (MCF7-miR526b, MCF7-miR655, MCF7-COX2, and SKBR3-miR526b) compared to controls (MCF7 and SKBR3). CoCl2-induced hypoxia in breast cancer further promotes HIF-1α mRNA and protein expression while reducing VHL expression (a negative HIF-1α regulator), especially in miRNA-high cell lines. Hypoxia enhances oxidative stress, epithelial to mesenchymal transition, cell migration, and vascular mimicry more prominently in MCF7-miR526b/MCF7-miR655 cell lines compared to MCF7 cells. Hypoxia promotes inflammatory and angiogenesis marker (COX-2, EP4, NFκB1, VEGFA) expression in all miRNA-high cells. Hypoxia upregulates miR526b/miR655 expression in MCF7 cells, thus observed enhancement of hypoxia-induced functions in MCF7 could be attributed to miR526b/miR655 upregulation. In silico bioinformatics analysis shows miR526b/miR655 regulate PTEN (a negative regulator of HIF-1α) and NFκB1 (positive regulator of COX-2 and EP4) expression by downregulation of transcription factors NR2C2, SALL4, and ZNF207. Hypoxia-enhanced functions in miRNA-high cells are inhibited by COX-2 inhibitor (Celecoxib), EP4 antagonist (ONO-AE3-208), and irreversible PI3K/Akt inhibitor (Wortmannin). This establishes that hypoxia enhances miRNA functions following the COX-2/EP4/PI3K/Akt pathways and this pathway can serve as a therapeutic target to abrogate hypoxia and miRNA induced functions in breast cancer. In situ, HIF-1α expression is significantly higher in human breast tumors (n = 96) compared to non-cancerous control tissues (n = 20) and is positively correlated with miR526b/miR655 expression. In stratified tumor samples, HIF-1α expression was significantly higher in ER-positive, PR-positive, and HER2-negative breast tumors. Data extracted from the TCGA database also show a strong correlation between HIF-1α and miRNA-cluster expression in breast tumors. This study, for the first time, establishes the dynamic roles of miR526b/miR655 in hypoxia.

Cytotoxic activity and anti-cancer potential of Ontario grown onion extracts against breast cancer cell lines

2018 ◽  
Vol 8 (3) ◽  
pp. 159 ◽  
Author(s):  
Meghan Fragis ◽  
Abdulmonem I. Murayyan ◽  
Suresh Neethirajan
Keyword(s):  
Breast Cancer ◽  
Cytotoxic Activity ◽  
Cell Lines ◽  
Cancer Cell ◽  
Breast Cancer Cell ◽  
Cancer Cell Lines ◽  
Breast Cancer Cell Lines ◽  
Cytotoxic Activities ◽  
Cancer Line ◽  
Mcf 7

Background: Breast cancer is the most commonly diagnosed cancer and the second leading cause of cancer deaths among Canadian women. Cancer management through changes in lifestyle, such as increased intake of foods rich in dietary flavonoids, have been shown to decrease the risk associated with breast, liver, colorectal, and upper-digestive cancers in epidemiologic studies. Onions are high in flavonoid content and one of the most common vegetables. Additionally, onions are used in most Canadian cuisines.Methods: We investigated the effect of five prominent Ontario grown onion (Stanley, Ruby Ring, LaSalle, Fortress, and Safrane) extracts on two subtypes of breast cancer cell lines: a triple negative breast cancer line MDA-MB-231 and an ER+ breast cancer line MCF-7.Results: These onion extracts elicited strong anti-proliferative, anti-migratory, and cytotoxic activities on both the cancer cell lines. Flavonoids present in these onion extracts induced apoptosis, cell cycle arrest in the G2/M phase, and a reduction in mitochondrial membrane potential at dose-dependent concentrations. Onion extracts were more effective against MDA-MB-231 compared to the MCF-7 cell line. Conclusion: In this study, we investigated the extracts synthesized from Ontario-grown onion varieties in inducing anti-migratory, cytostatic, and cytotoxic activities in two sub-types of human breast cancer cell lines. Anti-tumor activity of these extracts depends upon the varietal and can be formulated into nutraceuticals and functional foods for the wellbeing of cancer patients. Overall, the results suggest that onion extracts are a good source of flavonoids with anti-cancerous properties.Keywords: onion extracts; flavonoids; anti-proliferative; breast cancer; cytotoxic activity

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