scholarly journals Manipulating Estrogenic/Anti-Estrogenic Activity of Triphenylethylenes towards Development of Novel Anti-Neoplastic SERMs

2021 ◽  
Vol 22 (22) ◽  
pp. 12575
Author(s):  
Heba E. Elnakib ◽  
Marian M. Ramsis ◽  
Nouran O. Albably ◽  
Merna A. Vector ◽  
Jan J. Weigand ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Estrogen Receptor ◽  
Cell Line ◽  
Estrogenic Activity ◽  
Endometrial Adenocarcinoma ◽  
Metastatic Breast ◽  
Breast Cancer Cell Lines ◽  
The Novel ◽  
Potential Growth ◽  
Mcf 7

Selective estrogen receptor modulators (SERMs) act as estrogen receptor (ERα) agonists or antagonists depending on the target issue. Tamoxifen (TAM) (a non-steroidal triphenylethylene derivative) was the first SERM approved as anti-estrogen for the treatment of metastatic breast cancer. On the hunt for novel SERMs with potential growth inhibitory activity on breast cancer cell lines yet no potential to induce endometrial carcinoma, we designed and synthesized 28 novel TAM analogs. The novel analogs bear a triphenylethylene scaffold. Modifications on rings A, B, and C aim to attenuate estrogenic/anti-estrogenic activities of the novel compounds so they can potentially inhibit breast cancer and provide positive, beneficial estrogenic effects on other tissues with no risk of developing endometrial hyperplasia. Compound 12 (E/Z-1-(2-{4-[1-(4-Chloro-phenyl)-2-(4-methoxy-phenyl)-propenyl]-phenoxy}-ethyl)-piperidine) showed an appreciable relative ERα agonistic activity in a yeast estrogen screen (YES) assay. It successfully inhibited the growth of the MCF-7 cell line with GI50 = 0.6 µM, and it was approximately three times more potent than TAM. It showed no potential estrogenicity on Ishikawa endometrial adenocarcinoma cell line via assaying alkaline phosphatase (AlkP) activity. Compound 12 was tested in vivo to assess its estrogenic properties in an uterotrophic assay in an ovariectomized rat model. Compared to TAM, it induced less increase in wet uterine wet weight and showed no uterotrophic effect. Compound 12 is a promising candidate for further development due to its inhibition activity on MCF-7 proliferation with moderate AlkP activity and no potential uterotrophic effects. The in vitro estrogenic activity encourages further investigations toward potential beneficial properties in cardiovascular, bone, and brain tissues.

scholarly journals Integrative analysis of mRNA and miRNA profiles identifies miR-193 and miR-210 as potential regulatory biomarkers in different molecular subtypes of breast cancer

2020 ◽  
Author(s):  
Adriane Feijo Evangelista ◽  
Renato J Oliveira ◽  
Viviane A O Silva ◽  
Rene A D C Vieira ◽  
Rui M Reis ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cell Proliferation ◽  
Cell Line ◽  
Cell Lines ◽  
Breast Cancer Cell ◽  
Cancer Progression ◽  
Triple Negative ◽  
Molecular Subtypes ◽  
Breast Cancer Cell Lines ◽  
Mcf 7

Abstract Introduction: Breast cancer is the most frequently diagnosed malignancy among women. However, the role of microRNA expression in breast cancer progression is not fully understood. In this study we examined predictive interactions between differentially expressed miRNAs and mRNAs in breast cancer cell lines representative of the common molecular subtypes. Integrative bioinformatics analysis identified miR-193 and miR-210 as potential regulatory biomarkers of mRNA in breast cancer. Several recent studies have investigated these miRNAs in a broad range of tumors, but the mechanism of their involvement in cancer progression has not previously been investigated. Methods: The miRNA-mRNA interactions in breast cancer cell lines were identified by parallel expression analysis and miRNA target prediction programs. The expression profiles of mRNA and miRNAs from luminal (MCF-7, MCF-7/AZ and T47D), HER2 (BT20 and SK-BR3) and triple negative subtypes (Hs578T e MDA-MB-231) could be clearly separated by unsupervised analysis using HB4A cell line as a control. Breast cancer miRNA data from TCGA patients were grouped according to molecular subtypes and then used to validate these findings. Expression of miR-193 and miR-210 was investigated by miRNA transient silencing assays using the MCF7, BT20 and MDA-MB-231 cell lines. Functional studies included, xCELLigence system, ApoTox-Glo triplex, flow cytometry and transwell assays were performed to determine cell proliferation, cytotoxicity, apoptosis, migration and invasion, respectively. Results: The most evident effects were associated with cell proliferation after miR-210 silencing in triple negative subtype cell line MDA-MB-231. Using in silico prediction algorithms, TNFRSF10 was identified as one of the potential downstream targets for both miRNAs. The TNFRSF10C and TNFRSF10D mRNA expression inversely correlated with the expression levels of miR-193 and miR210 in breast cell lines and breast cancer patients, respectively. Other potential regulated genes whose expression also inversely correlated with both miRNAs were CCND1, a mediator on invasion and metastasis, and the tumor suppressor gene RUNX3. Conclusion: In summary, our findings identify miR-193 and miR-210 as potential regulatory miRNA in different molecular subtypes of breast cancer and suggest that miR-210 may have specific role in MDA-MB-231 proliferation. Our results highlight important new downstream regulated targets that may serve as promising therapeutic pathways for aggressive breast cancers.

scholarly journals Molecular and chemical characterization by Fourier transform infrared spectroscopy of human breast cancer cells with estrogen receptor expressed and not expressed

2010 ◽  
Vol 24 (5) ◽  
pp. 501-510 ◽  
Author(s):  
Leila Büttner Mostaço-Guidolin ◽  
Luciana Sayuri Murakami ◽  
Marina Ribeiro Batistuti ◽  
Auro Nomizo ◽  
Luciano Bachmann
Keyword(s):  
Breast Cancer ◽  
Fatty Acids ◽  
Estrogen Receptor ◽  
Cell Lines ◽  
Human Breast Cancer ◽  
Breast Cancer Cells ◽  
Chemical Characterization ◽  
Breast Cancer Cell Lines ◽  
Human Breast ◽  
Mcf 7

The present study was designed to identify and compare the infrared absorption spectra of two human breast cancer cell lines: MCF-7 (estrogen receptor expressed, ER+) and SKBr3 (estrogen receptor non-expressed, ER–). Comparison between SKBr3 and MCF-7 cells revealed differences in the following absorption band areas: 1087 cm–1(DNA), 1397 cm–1(CH3), 1543 cm–1(amide II), 1651 cm–1(amide I), 2924 cm–1(fatty acids). Additionally, peak shifts were observed at 1122 cm–1(RNA), 1397 cm–1(CH3), 1651 cm–1(amide I), 2851 cm–1(fatty acids) and 2962 cm–1(fatty acids). An analysis of the ratio between band areas was conducted, in order to obtain an index that could effectively distinguish between these two cell lines. The following ratios were found: 1650 cm–1/1540 cm–1, 1650 cm–1/1740 cm–1, 1650 cm–1/1084 cm–1and 1120 cm–1/1084 cm–1. This work demonstrates that it is possible to distinguish between MCF-7 and SKBr3 cells through differences in their FTIR spectra. This work enables distinction between two cell lines from the same breast cancer.

scholarly journals Cannabinoid Combination Induces Cytoplasmic Vacuolation in MCF-7 Breast Cancer Cells

Molecules ◽  
2020 ◽  
Vol 25 (20) ◽  
pp. 4682
Author(s):  
Recardia Schoeman ◽  
Natasha Beukes ◽  
Carminita Frost
Keyword(s):  
Breast Cancer ◽  
Endoplasmic Reticulum ◽  
Cell Line ◽  
Cancer Cell ◽  
Breast Cancer Cell Lines ◽  
Effect Analysis ◽  
Cytoplasmic Vacuolation ◽  
Cycle Arrest ◽  
Median Effect Analysis ◽  
Mcf 7

This study evaluated the synergistic anti-cancer potential of cannabinoid combinations across the MDA-MB-231 and MCF-7 human breast cancer cell lines. Cannabinoids were combined and their synergistic interactions were evaluated using median effect analysis. The most promising cannabinoid combination (C6) consisted of tetrahydrocannabinol, cannabigerol (CBG), cannabinol (CBN), and cannabidiol (CBD), and displayed favorable dose reduction indices and limited cytotoxicity against the non-cancerous breast cell line, MCF-10A. C6 exerted its effects in the MCF-7 cell line by inducing cell cycle arrest in the G2 phase, followed by the induction of apoptosis. Morphological observations indicated the induction of cytoplasmic vacuolation, with further investigation suggesting that the vacuole membrane was derived from the endoplasmic reticulum. In addition, lipid accumulation, increased lysosome size, and significant increases in the endoplasmic reticulum chaperone protein glucose-regulated protein 78 (GRP78) expression were also observed. The selectivity and ability of cannabinoids to halt cancer cell proliferation via pathways resembling apoptosis, autophagy, and paraptosis shows promise for cannabinoid use in standardized breast cancer treatment.

scholarly journals Compounds From the Root of Pueraria peduncularis (Grah. ex Benth.) Benth. and Their Antitumor Effects

2019 ◽  
Vol 14 (11) ◽  
pp. 1934578X1988252
Author(s):  
Huabao Chen ◽  
Yong Qian ◽  
Xiaomin Zhao ◽  
Tianxing Lv ◽  
Bin Wang ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Lung Adenocarcinoma ◽  
Cell Line ◽  
Cancer Cell ◽  
Breast Cancer Cell ◽  
Breast Cancer Cell Lines ◽  
Root Extract ◽  
Antitumor Effects ◽  
Wide Range ◽  
Mcf 7

Pueraria peduncularis belongs to the genus Pueraria DC., and has a wide range of medicinal and agricultural values. Previous studies have shown that methanol extracts of P. peduncularis had broad range bioactivities against different pests such as insects, phytopathogens, and snails; however, the specific studies with regard to active compounds against these pests have not been reported. In the current study, we systematically assessed the effects of P. peduncularis root extract against cancer cells, and we also isolated, purified, and analyzed the active ingredients of 8 different compounds from the root of P. peduncularis. To the best of our knowledge, coumestrol (compound 1), lupinalbin A (compound 2), wighteone (compound 6), and erythrinin C (compound 4) were the first isolated from the P. peduncularis root in our study. The extract of the P. peduncularis root had a significantly strong cytotoxic activity on the lung adenocarcinoma cell line A549 (31.0%) and breast cancer cell line MCF-7 (33.0%), respectively. Lupinalbin A (compound 2), erythrinin C (compound 4), pedunsaponin A (compound 7), and pedunsaponin C (compound 8) had more than 40% inhibitory effects on the lung adenocarcinoma line A549. Whereas erythrinin C (compound 4) and pedunsaponin C inhibited more than 47% breast cancer cell lines MCF-7. These results indicate that P. peduncularis is rich in anticancer substances that laid the foundation for a further understanding of P. peduncularis and need to be further explored for other diseases.

scholarly journals A Combination of an Antimitotic and a Bromodomain 4 Inhibitor Synergistically Inhibits the Metastatic MDA-MB-231 Breast Cancer Cell Line

2019 ◽  
Vol 2019 ◽  
pp. 1-13 ◽  
Author(s):  
Thandi Mqoco ◽  
André Stander ◽  
Anna-Mart Engelbrecht ◽  
Anna M Joubert
Keyword(s):  
Breast Cancer ◽  
Cancer Cells ◽  
Cell Line ◽  
Cancer Cell ◽  
Breast Cancer Cell ◽  
Breast Cancer Cells ◽  
Chemotherapeutic Agents ◽  
Breast Cancer Cell Lines ◽  
Mcf 7

Current chemotherapeutic agents have many side effects and are toxic to normal cells, providing impetus to identify agents that can effectively eliminate tumorigenic cells without damaging healthy cells. The aim of this study was to examine whether combining a novel BRD4 inhibitor, ITH-47, with the antimitotic estradiol analogue, ESE-15-ol, would have a synergistic effect on inhibiting the growth of two different breast cancer cell lines in vitro. Our docking and molecular dynamics studies showed that compared to JQ1, ITH-47 showed a similar binding mode with hydrogen bonds forming between the ligand nitrogens of the pyrazole, ASN99, and water of the BRD4 protein. Data from cell growth studies revealed that the GI50 of ITH-47 and ESE-15-ol after 48 hours of exposure was determined to be 15 μM and 70 nM, respectively, in metastatic MDA-MB-231 breast cancer cells. In tumorigenic MCF-7 breast cancer cells, the GI50 of ITH-47 and ESE-15-ol was 75 μM and 60 nM, respectively, after 48 hours of exposure. Furthermore, the combination of 7.5 μM and 14 nM of ITH-47 and ESE-15-ol, respectively, resulted in 50% growth inhibition of MDA-MB-231 cells resulting in a synergistic combination index (CI) of 0.7. Flow cytometry studies revealed that, compared to the control, combination-treated MDA-MB-231 cells had significantly more cells present in the sub-G1 phase and the combination treatment induced apoptosis in the MDA-MB-231 cells. Compared to vehicle-treated cells, the combination-treated cells showed decreased levels of the BRD4, as well as c-Myc protein after 48 hours of exposure. In combination, the selective BRD4 inhibitor, ITH-47, and ESE-15-ol synergistically inhibited the growth of MDA-MB-231 breast cancer cells, but not of the MCF-7 cell line. This study provides evidence that resistance to BRD4 inhibitors may be overcome by combining inhibitors with other compounds, which may have treatment potential for hormone-independent breast cancers.

Translational cell study exploring the role of estrogen receptor β expression as a predictive and/or prognostic factor in breast cancer patients

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. e22185-e22185
Author(s):  
S. Saji ◽  
N. Honma ◽  
M. Hirose ◽  
S. Hayashi ◽  
K. Kuroi
Keyword(s):  
Breast Cancer ◽  
Estrogen Receptor ◽  
Cell Line ◽  
Cancer Patients ◽  
Triple Negative ◽  
Breast Cancer Patients ◽  
Her 2 ◽  
Mcf 7 ◽  
Cell Study ◽  
Positive Breast Cancer

e22185 Background: We have reported that positive expression of Estrogen receptor β (ERβ) was associated with better prognosis in the early breast cancer patients treated with adjuvant tamoxifen monotherapy (J Clin Oncol. 2008). In addition, this was also true in the ERα-negative/PR-negative/Her-2 negative patients. We explored the biological impact of ERβ in breast cancer cell lines to determine whether these observations were due to its prognostic power or predictive power of response to the therapy. Methods: Since MCF-7 cell was ERβ-negative ERα-positive cell line, we established two stable clones of MCF-7 by introducing ERβ expression vector (β-clone 1, β-clone 2) as the model of ERβ-positive ERα-positive breast cancer. MDA-MB 231 cell was used as ERβ-positive triple-negative cell line. These cells were subjected to proliferation, expression and functional analysis. Results: In western blotting, both β-clone 1 and clone 2 showed decreased expression of PR and Her-2 than parent MCF-7, although there were no differences in ERα expression. Expression of ERβ decreased estradiol (E2) induced proliferation ability and rate of cells in S-phase cycle. PPT (ERα-specific agonist) and DPN (ERβ-specific agonist) did not show any difference in response, and IC 50 for 4 OH-tamoxifen and fulvestrant did not differ among MCF-7, β-clone 1 and clone 2 (0.05–0.1 μM). Whereas, cell death due to deprivation of E2 from 1nM to 1pM was more frequently observed in ERβ-expressing clones than in parent MCF-7 cell. These cell deaths did not involve standard apoptosis pathway with caspase-3/7 activation and PARP cleavage. E2, DPN and PPT did not affect the proliferation of ERβ-positive triple negative MDA-MB 231 cell, and IC 50 for 4-OH tamoxifen was too high (8 μM) to be achieved in clinical pharmacological dose. Conclusions: From our cell study, better prognosis of ERβ-positive breast cancer patient who treated with adjuvant tamoxifen is mainly due to its own favorable biological behavior. However, this prognostic impact may include the favorable response to the treatment, when we use estrogen-deprivation therapy such as aromatase inhibitors (AIs). Additional clinical study in AI users would be required to address this issue. No significant financial relationships to disclose.

scholarly journals Substituted Thiazole Linked Murrayanine-Schiff�s Base Derivatives as Potential Anti-Breast Cancer Candidates: Future EGFR Kinase Inhibitors

2017 ◽  
Vol 9 (3) ◽  
Author(s):  
Debarshi Kar Mahapatra ◽  
Devashish Das ◽  
Ruchi Shivhare
Keyword(s):  
Breast Cancer ◽  
Cell Line ◽  
Kinase Inhibitors ◽  
Analytical Techniques ◽  
Docking Study ◽  
Breast Cancer Cell Lines ◽  
Synthetic Approach ◽  
Hybrid Molecules ◽  
Anti Cancer ◽  
Mcf 7

Cancer is the second leading causes of mortality across the planet which has had affected millions. In spite of massive efforts in producing new molecules and chemotherapeutic approaches for managing cancer, it continued to be the global threat. Small hybrid molecules have gained popularity in chemotherapy due to their potential and smart characteristics in modulating biological targets. The present research attempts in developing few novel hybridized derivatives of murrayanine (an active carbazole derivative) by the semi-synthetic approach to form substituted thiazole linked murrayanine-Schiffs base derivatives. The protocol involved murrayanine 1 as the template material for constructing a hybridized Schiffs base intermediate 3, which further by Hantzchs cyclization was subsequently converted to various hybridized thiazoles analogs 5a-5f. The purity of the synthesized compounds was ascertained by sophisticated analytical techniques. The anti-cancer potential was screened against breast cancer cell lines; MCF-7 and MDA-MB-231 by Sulforhodamine B (SRB) assay. The compound 5b displayed most potent anti-proliferative activity with IC50 values of 23.41?M against MCF-7 cell line and 32.15?M against MDA-MB-231 cell line. It has been observed that analogs having electron withdrawing substituents exhibited pronounced anticancer activity. The docking study was performed by Autodock Vina where the results were found to be in full agreement with the cytotoxic study, depicting that the probable cytotoxic outcome by EGFR inhibitory mechanism. The study revealed the potential of novel hybridized derivatives as active anti-breast cancer candidates. The research will encourage (medicinal) chemists in rationally designing of semi-synthetic analogs of a heterocyclic prototype having pronounced anti-cancer activity.

scholarly journals HUMAN BREAST TUMOUR CELLS VIABILITY EFFECT OF AFRICAN DIOSCOREA ROTUNDATA TUBER EXTRACTS IN MCF-7 AND MDA-MB231 CELL LINES

2020 ◽  
Author(s):  
Joy Ifunanya Odimegwu ◽  
Olukemi Abiodun Odukoya ◽  
Alejandro Español ◽  
Maria Elena Sales
Keyword(s):  
Breast Cancer ◽  
Cell Lines ◽  
Metastatic Breast ◽  
Tumour Cells ◽  
Breast Cancer Cell Lines ◽  
Maximal Effect ◽  
Dioscorea Rotundata ◽  
Ethanolic Extracts ◽  
Dioscorea Species ◽  
Mcf 7

ABSTRACTObjectiveWe aim to test the efficacy of edible Dioscorea species grown and consumed in Nigeria, Africa on two breast cancer cell lines; MCF-7 and MDA-MB231 derived from a luminal and a triple-negative breast cancer (TNBC) respectively and to confirm safety in non-tumour cells MCF-10A using a well established cytotoxic compound paclitaxel as a standard. Metastatic breast cancer is a prevalent cause of mortality in women around the world. Breast cancer therapies have greatly advanced in recent years, but many patients develop cancer re-occurrence and metastasis and subsequently yield to the disease because of chemoresistance.MethodsEthanolic extracts of Dioscorea rotundata boiled and raw (DiosB and DiosR) respectively were chemically analysed for the presence of diosgenin using HPLC and the cytotoxic activity of the extracts were tested on MCF-7, MDA-MB-231 and MCF-10A cells In vitro by MTT assay.ResultsDiosB and DiosR extracts showed a higher maximal effect on MCF-7 cells than on MDA-MB231 after 24 h and 48 h treatments (p<0.0001 and p<0.05 respectively). DiosR, if applied at a range between 50-70 g/ml, can be effective to reduce breast tumor cell viability without affecting non tumorigenic MCF-10A cells either at 24 h or at 48 h. DiosB showed an IC50 of 38.83μg/ml while DiosR showed an IC50 of 41.80μg/ml.ConclusionThese results show that ethanolic extracts of Dioscorea rotundata tubers could be used effectively to treat breast cancer tumors and this is in sync with its diosgenin content as other Dioscorea species applied for similar treatments in Asia and elsewhere.

scholarly journals Integrative analysis of mRNA and miRNA profiles identifies miR-193 and miR-210 as potential regulatory biomarkers in different molecular subtypes of breast cancer

2021 ◽  
Author(s):  
Adriane Feijo Evangelista ◽  
Renato J Oliveira ◽  
Viviane A O Silva ◽  
Rene A D C Vieira ◽  
Rui M Reis ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cell Proliferation ◽  
Cell Line ◽  
Cell Lines ◽  
Breast Cancer Cell ◽  
Cancer Progression ◽  
Triple Negative ◽  
Molecular Subtypes ◽  
Breast Cancer Cell Lines ◽  
Mcf 7

Abstract Background: Breast cancer is the most frequently diagnosed malignancy among women. However, the role of microRNA (miRNA) expression in breast cancer progression is not fully understood. In this study we examined predictive interactions between differentially expressed miRNAs and mRNAs in breast cancer cell lines representative of the common molecular subtypes. Integrative bioinformatics analysis identified miR-193 and miR-210 as potential regulatory biomarkers of mRNA in breast cancer. Several recent studies have investigated these miRNAs in a broad range of tumors, but the mechanism of their involvement in cancer progression has not previously been investigated.Methods: The miRNA-mRNA interactions in breast cancer cell lines were identified by parallel expression analysis and miRNA target prediction programs. The expression profiles of mRNA and miRNAs from luminal (MCF-7, MCF-7/AZ and T47D), HER2 (BT20 and SK-BR3) and triple negative subtypes (Hs578T e MDA-MB-231) could be clearly separated by unsupervised analysis using HB4A cell line as a control. Breast cancer miRNA data from TCGA patients were grouped according to molecular subtypes and then used to validate these findings. Expression of miR-193 and miR-210 was investigated by miRNA transient silencing assays using the MCF7, BT20 and MDA-MB-231 cell lines. Functional studies included, xCELLigence system, ApoTox-Glo triplex assay, flow cytometry and transwell inserts were performed to determine cell proliferation, cytotoxicity, apoptosis, migration and invasion, respectively.Results: The most evident effects were associated with cell proliferation after miR-210 silencing in triple negative subtype cell line MDA-MB-231. Using in silico prediction algorithms, TNFRSF10 was identified as one of the potential regulated downstream targets for both miRNAs. The TNFRSF10C and TNFRSF10D mRNA expression inversely correlated with the expression levels of miR-193 and miR210 in breast cell lines and breast cancer patients, respectively. Other potential regulated genes whose expression also inversely correlated with both miRNAs were CCND1, a known mediator on invasion and metastasis, and the tumor suppressor gene RUNX3.Conclusions: In summary, our findings identify miR-193 and miR-210 as potential regulatory miRNA in different molecular subtypes of breast cancer and suggest that miR-210 may have a specific role in MDA-MB-231 proliferation. Our results highlight important new downstream regulated targets that may serve as promising therapeutic pathways for aggressive breast cancers

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