Effect of pesticides on estrogen receptor transactivation in vitro: A comparison of stable transfected MVLN and transient transfected MCF-7 cells

2005 ◽  
Vol 244 (1-2) ◽  
pp. 20-30 ◽  
Author(s):  
Eva C. Bonefeld-Jorgensen ◽  
Heidi T. Grünfeld ◽  
Irene M. Gjermandsen
Keyword(s):  
Estrogen Receptor ◽  
Receptor Transactivation ◽  
Mcf 7

scholarly journals Concanavalin-A shows synergistic cytotoxicity with tamoxifen via inducing apoptosis in estrogen receptor-positive breast cancer: In vitro and molecular docking studies

2021 ◽  
Author(s):  
Mohamed Elshal ◽  
Norhan Eid ◽  
Ibrahim El-Sayed ◽  
Wael El-Sayed ◽  
Ahmed Ali Al-Karmalawy
Keyword(s):  
Breast Cancer ◽  
Estrogen Receptor ◽  
Molecular Docking ◽  
Concanavalin A ◽  
Combined Treatment ◽  
Con A ◽  
Synergistic Cytotoxicity ◽  
Mcf 7 ◽  
Positive Breast Cancer

Background: Tamoxifen (TAM) is the main treatment of estrogen receptor (ER)-positive breast cancer, however; its adverse effects and development of resistance hinder its use. Concanavalin A (Con A) is a mannose/glucose-binding lectin that has been reported to induce apoptosis in a variety of cell lines. Methods: Therefore, we aimed to elucidate the effects of Con A on TAM-induced cell death in ERα positive cell line (MCF-7) and to identify the potential underlying molecular mechanisms using in silico and in vitro techniques. Results: Our results demonstrated that combined treatment with Con A and TAM reduced the expression of ERα, which showed clear synergistic effects on inhibiting the cell viability of MCF-7 cells. Interestingly, the combined treatment induces G1 phase arrest and reduces cyclin D1 activity while increasing apoptosis and autophagy as indicated by decreasing the expression level of anti-apoptosis gene BCl-2 and increased apoptosis/autophagic gene BNIP3. Molecular docking was conducted to evaluate the binding affinity of Con A towards ERα, and it revealed its potential activity as an ERα antagonist. Our data further indicated that Con A administration increased the drug reduction index of TAM. Conclusion: Overall, our findings suggested that Con A could be used as an adjuvant agent with TAM to improve its effectiveness as an anticancer agent while minimizing its side effects.

scholarly journals Mitochondria-targeted triphenylphosphonium-based compounds do not affect estrogen receptor α

PeerJ ◽  
2020 ◽  
Vol 8 ◽  
pp. e8803
Author(s):  
Ludmila A. Zinovkina ◽  
Alina K. Galivondzhyan ◽  
Anastasia S. Prikhodko ◽  
Ivan I. Galkin ◽  
Roman A. Zinovkin
Keyword(s):  
Cell Cycle ◽  
Estrogen Receptor ◽  
Real Time ◽  
Cell Cycle Progression ◽  
Expression Vector ◽  
Estrogen Receptor Α ◽  
Luciferase Expression ◽  
Cycle Progression ◽  
Mcf 7

Background Targeting negatively charged mitochondria is often achieved using triphenylphosphonium (TPP) cations. These cationic vehicles may possess biological activity, and a docking study indicates that TPP-moieties may act as modulators of signaling through the estrogen receptor α (ERα). Moreover, in vivo and in vitro experiments revealed the estrogen-like effects of TPP-based compounds. Here, we tested the hypothesis that TPP-based compounds regulate the activity of ERα. Methods We used ERa-positive and ERα-negative human breast adenocarcinoma cell lines (MCF-7 and MDA-MB-231, respectively). Cell proliferation was measured using a resazurin cell growth assay and a real-time cell analyzer assay. Cell cycle progression was analyzed using flow cytometry. Real-time PCR was used to assess mRNA expression of endogenous estrogen-responsive genes. Luciferase activity was measured to evaluate transcription driven by estrogen-responsive promoters in cells transfected with an estrogen response element (ERE)3-luciferase expression vector. Results The TPP-based molecules SkQ1 and C12TPP, as well as the rhodamine-based SkQR1, did not increase the proliferation or alter the cell cycle progression of MCF-7 cells. In contrast, 17β estradiol increased the proliferation of MCF-7 cells and the proportion of cells in the S/G2/M-phases of the cell cycle. TPP-based compounds did not affect the induction of transcription of an ERE-luciferase expression vector in vitro, and SkQ1 did not alter the levels of expression of estrogen-dependent genes encoding GREB1, TFF1, COX6, and IGFBP4. Conclusion TPP-based compounds do not possess properties typical of ERα agonists.

scholarly journals Interaction of Vault Particles with Estrogen Receptor in the MCF-7 Breast Cancer Cell

1998 ◽  
Vol 141 (6) ◽  
pp. 1301-1310 ◽  
Author(s):  
Ciro Abbondanza ◽  
Valentina Rossi ◽  
Annarita Roscigno ◽  
Luigi Gallo ◽  
Angela Belsito ◽  
...  
Keyword(s):  
Estrogen Receptor ◽  
Glucocorticoid Receptors ◽  
Sodium Molybdate ◽  
Nuclear Extract ◽  
Supernatant Fraction ◽  
Cdna Clones ◽  
Major Vault Protein ◽  
Estradiol Treatment ◽  
Mcf 7

A 104-kD protein was coimmunoprecipitated with the estrogen receptor from the flowtrough of a phosphocellulose chromatography of MCF-7 cell nuclear extract. mAbs to this protein identified several cDNA clones coding for the human 104-kD major vault protein. Vaults are large ribonucleoprotein particles of unknown function present in all eukaryotic cells. They have a complex morphology, including several small molecules of RNA, but a single protein species, the major vault protein, accounts for >70% of their mass. Their shape is reminiscent of the nucleopore central plug, but no proteins of known function have been described to interact with them. Western blot analysis of vaults purified on sucrose gradient showed the presence of estrogen receptor co-migrating with the vault peak. The AER317 antibody to estrogen receptor coimmunoprecipitated the major vault protein and the vault RNA also in the 20,000 g supernatant fraction. Reconstitution experiments of estrogen receptor fragments with the major vault protein mapped the site of the interaction between amino acids 241 and 280 of human estrogen receptor, where the nuclear localization signal sequences are located. Estradiol treatment of cells increased the amount of major vault protein present in the nuclear extract and coimmunoprecipitated with estrogen receptor, whereas the anti-estrogen ICI182,780 had no effect. The hormone-dependent interaction of vaults with estrogen receptor was reproducible in vitro and was prevented by sodium molybdate. Antibodies to progesterone and glucocorticoid receptors were able to coimmunoprecipitate the major vault protein. The association of nuclear receptors with vaults could be related to their intracellular traffic.

scholarly journals A potential estrogen receptor inhibitor compound 34 induces apoptosis via ROS-independent intrinsic apoptosis in MCF-7 cells

2019 ◽  
Vol 14 (1) ◽  
pp. 1-8
Author(s):  
Ruru Ding ◽  
Ziying Zhu ◽  
Mengting Teng ◽  
Lin Ma ◽  
Jiaying Hu ◽  
...  
Keyword(s):  
Estrogen Receptor ◽  
Video Clip ◽  
Docking Studies ◽  
Intrinsic Apoptosis ◽  
Estrogen Receptor Positive ◽  
Full Screen ◽  
Apoptosis Related Protein ◽  
Induced Apoptosis ◽  
Mcf 7

This study aimed to investigate the anti-tumor effects of compound 34 on MCF-7 cells in vitro, and explore its mechanisms. MTT results showed that compound 34 selectively inhibited estrogen receptor-positive cells proliferation. Hoechst 33342 staining showed nuclear pyknosis, nuclear debris associated with apoptotic bodies. JC-1 staining showed the loss of mitochondrial membrane potential. Although compound 34 increased intracellular reactive oxygen species (ROS), compound 34-induced apoptosis was not prevented by pretreatment with ROS scavengers. Western blotting showed apoptosis-related protein like cytochrome c and cleaved PARP protein increased. Furthermore, docking studies exhibited that compound 34 could bind into ERα. In summary, compound 34 selectively inhibited estrogen receptor positive cells proliferation and induced apoptosis in MCF-7 cells via ROS-independent intrinsic apoptosis in MCF-7 cells. It may be a potential targeted drug of estrogen receptor for therapeutic application of breast cancer. Video Clip of Methodology: Assay of Cell Proliferation: 5 min 5 sec   Full Screen   Alternate  

scholarly journals 2-Phenylacetamide Isolated from the Seeds of Lepidium apetalum and Its Estrogen-Like Effects In Vitro and In Vivo

Molecules ◽  
2018 ◽  
Vol 23 (9) ◽  
pp. 2293 ◽  
Author(s):  
Mengnan Zeng ◽  
Meng Li ◽  
Miao Li ◽  
Beibei Zhang ◽  
Benke Li ◽  
...  
Keyword(s):  
Estrogen Receptor ◽  
Inductive Effect ◽  
Uterine Weight ◽  
Immature Female ◽  
Main Compound ◽  
Material Basis ◽  
Weight Test ◽  
Mcf 7

The aim of this study was to investigate the estrogen-like effects of 2-phenylacetamide (PA), which is the main compound isolated from the seeds of Lepidium apetalum Willd (LA). Results showed that LA and PA could promote the proliferation of MCF-7 cells. The mouse uterine weight test showed that, LA and PA could increase the uterus index of immature female mice, and the levels of luteinizing hormone (LH) and estrogen (E2). LA could increase the expression of ERα and ERβ, while PA could increase the expression of ERα, ERβ and GPR30 in the uterus and MCF-7 cells. In addition, co-incubation of the estrogen receptor blocker with LA or PA abolished the inductive effect of the proliferation. PA has estrogenic activities and was the material basis of LA that played the estrogenic effect. LA and PA might be used for the treatment of perimenopause syndrome in a novel application.

scholarly journals Vitamin D Compounds PRI-2191 and PRI-2205 Enhance Anastrozole Activity in Human Breast Cancer Models

2021 ◽  
Vol 22 (5) ◽  
pp. 2781
Author(s):  
Beata Filip-Psurska ◽  
Mateusz Psurski ◽  
Artur Anisiewicz ◽  
Patrycja Libako ◽  
Ewa Zbrojewicz ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Vitamin D ◽  
Estrogen Receptor ◽  
Enzyme Inhibition ◽  
Active Metabolite ◽  
Synthetic Analog ◽  
Aromatase Activity ◽  
Therapeutic Effects ◽  
Mcf 7

1,25-Dihydroxycholecalciferol, the hormonally active vitamin D3 metabolite, is known to exhibit therapeutic effects against breast cancer, mainly by lowering the expression of estrogen receptors and aromatase activity. Previously, the safety of the vitamin D active metabolite (24R)-1,24-dihydroxycholecalciferol (PRI-2191) and 1,25(OH)2D3 analog PRI-2205 was tested, and the in vitro activity of these analogs against different cancer cell lines was studied. We determined the effect of the two vitamin D compounds on anastrozole (An) activity against breast cancer based on antiproliferative activity, ELISA, flow cytometry, enzyme inhibition potency, PCR, and xenograft study. Both the vitamin D active metabolite and synthetic analog regulated the growth of not only estrogen receptor-positive cells (T47D and MCF-7, in vitro and in vivo), but also hormone-independent cancer cells such as SKBR-3 (HER-2-positive) and MDA-MB-231 (triple-negative), despite their relatively low VDR expression. Combined with An, PRI-2191 and PRI-2205 significantly inhibited the tumor growth of MCF-7 cells. Potentiation of the antitumor activity in combined treatment of MCF-7 tumor-bearing mice is related to the reduced activity of aromatase by both An (enzyme inhibition) and vitamin D compounds (switched off/decreased aromatase gene expression, decreased expression of other genes related to estrogen signaling) and by regulation of the expression of the estrogen receptor ERα and VDR.

scholarly journals Cytotoxic Activity on MCF-7 Cells and in Silico Study of Sapogenin Steroids From Trigonella foenum-graecum L.

2017 ◽  
Vol 6 (1) ◽  
pp. 1
Author(s):  
Kurnia Agustini ◽  
Firdayani Firdayani ◽  
Churiyah Churiyah
Keyword(s):  
Breast Cancer ◽  
Estrogen Receptor ◽  
Binding Affinity ◽  
Breast Cancer Cell Line ◽  
Estrogen Receptor Alpha ◽  
Cancer Cell Line ◽  
Ethyl Acetate Fraction ◽  
Trigonella Foenum Graecum ◽  
Mcf 7

Trigonella foenum-graecum (TFG) is one of medicinal plants containing several steroidal sapogenins, such as diosgenin, yamogenin, gitogenin, tigogenin and trigoneoside, and also alkaloid trigonellin and some flavonoids such as vitexin, isovitexin, orientin, isoorientin, which has many activities, such as antidiabetic, estrogenic, and also anticancer.  As phytoestrogen, TFG was predicted to have potency as Selective Estrogen Receptor Modulators (SERMs) which is used for hormonal-dependent breast cancer treatment. This experiment was carried out to investigate interaction of some sapogenin steroids and flavonoids in TFG to estrogen receptor alpha (ERα) and its activity to breast cancer cell line as confirmation. In silico prediction was carried out to investigate their estrogenic activity by analyzing their binding affinity to ERα using AutoDock Vina program. In vitro activity confirmation of TFG extract and its fractions were carried out using MTT assay on Erα-positive human breast cancer cell line, MCF-7.  Results showed that free binding energies of diosgenin and yamogenin were -6.4 kcal/mol, estradiol was -6.0 kcal/mol, and tamoxifen was -5.1 kcal/mol.  While cytotoxicity assay showed that ethyl acetate fraction gave the lowest IC50 of 41.81 ppm, with total steroid content of 20.03 ppm.  From these results, we can conclude that diosgenin and yamogenin have greater binding affinity to ERα comparing to estradiol and tamoxifen.  In vitro assay confirmation showed that ethyl acetate fraction has cytotoxic effect on MCF-7 cells.Keywords: Trigonella foenum-graecum, sapogenin steroids, MCF-7, estrogen receptor alpha, binding affinity

scholarly journals Evaluation of estrogenic potential by herbal formula, HPC 03 for in vitro and in vivo

Reproduction ◽  
2018 ◽  
Vol 155 (2) ◽  
pp. 103-113 ◽  
Author(s):  
Bo Yoon Chang ◽  
Dae Sung Kim ◽  
Hye Soo Kim ◽  
Sung Yeon Kim
Keyword(s):  
Estrogen Receptor ◽  
Ovariectomized Rats ◽  
Herbal Formula ◽  
Mineral Density ◽  
Bone Mineral Density Loss ◽  
Ovx Rats ◽  
Estrogenic Potential ◽  
Mcf 7

HPC 03 is herbal formula that consists of extracts from Angelica gigas, Cnidium officinale Makino and Cinnamomum cassia Presl. The present study evaluated the estrogenic potential of HPC 03 by using in vitro and in vivo models. The regulatory mechanisms of HPC 03 in estrogen-dependent MCF-7 cells were assessed. HPC 03 induced the proliferation of estrogen receptor-positive MCF-7 cells, and the proliferation was blocked by the addition of the estrogen antagonist tamoxifen. The estrogen receptorα/β luciferase activities were significantly increased by HPC 03 treatment, which also increased the mRNA expression of the estrogen-responsive genes Psen2, Pgr and Ctsd. Also, we evaluated the ameliorative effects of HPC 03 on menopausal symptoms in ovariectomized rats. HPC 03 treatment in OVX rats significantly affected the uterine weight, increased the expression of estrogen-responsive genes Pgr and Psen2 in uterus, increased bone mineral density loss in the femur and inhibited body weight increase. Serum E2, collagen type 1 and osteocalcin were significantly increased, while serum LH, FSH and ALP were decreased compared with OVX rats. HPC 03 may be a promising candidate for the treatment of menopause, but further research is necessary to determine whether the observed effects also occur in humans.

scholarly journals Design and Synthesis of Novel Chalcone-Phenylpyranone Derivatives as Estrogen Receptor Modulators

Proceedings ◽  
2018 ◽  
Vol 9 (1) ◽  
pp. 30
Author(s):  
Pritam N. Dube ◽  
Yogita B. Thombare ◽  
Vivekanand A. Chatpalliwar
Keyword(s):  
Breast Cancer ◽  
Estrogen Receptor ◽  
Docking Study ◽  
Estrogen Receptor Α ◽  
Side Chain ◽  
Design And Synthesis ◽  
Estrogen Receptor Modulators ◽  
Receptor Modulators ◽  
Mcf 7

Selective estrogen receptor modulators (SERMs) are a class of drugs that act on the estrogen receptor (ER). SERMs are used for treatment and reduction of risk of breast cancer. Herewith we had designed, synthesized, and evaluated chalcone-phenylpyran-2-one derivatives bearing a N,N-dimethyl ethylamine side chain for their anti-breast cancer activity on MCF-7 and Zr-75-1 cell lines in-vitro. The pharmacological data indicated that most of tested compounds showed moderate to significant cytotoxicity and high selectivity toward the estrogen receptor. The Structure activity relationaship analyses indicated that compounds 5f with 2,6-dichloro substitution was more effective. Docking study was performed to predict binding orientation towards the estrogen receptor-α.

Sign in / Sign up

Export Citation Format

Share Document