scholarly journals Salicin a promising ER, PR and HER2 binding molecule proving lethal against Hormone + and triple negative breast cancer cells

2021 ◽  
Vol 12 (1) ◽  
pp. 73-83
Author(s):  
Mrudul Pravinbhai Vekaria ◽  
Pravin Tirgar
Keyword(s):  
Breast Cancer ◽  
Cancer Cells ◽  
Triple Negative Breast Cancer ◽  
Mechanism Of Action ◽  
Breast Cancer Cells ◽  
Triple Negative ◽  
Minimum Energy ◽  
Good Choice ◽  
Breast Cancer Cell Lines ◽  
Mcf 7

Therapeutics against breast cancer is a major research field, due to inefficiency or partial efficiency of existing therapeutics.  An urge to discover better therapeutics always persists. Our objective is to study salicin against breast cancer cells, in order to find its therapeutic properties. To study the effect of salicin on breast cancer cells, we performed MTT assay on MCF-7 (hormone positive) and MDA-MB-231 (triple negative) breast cancer cell lines, we did brine shrimp lethality test (BSLT) assay to see the lethal effects of salicin. By the help of bioinformatics we tried to locate the targets that delineate salicin activity. Salicin was docked with estrogen receptor (ER), progesterone receptor (PR) and Human epidermal growth factor receptor 2 (HER2) to study its binding efficiency and possible targets of salicin. Salicin remarkably reduces cell viability both in MCF-7 and MDA-MB-231, along with being lethal to brine shrimps. These results together opine that salicin can be an effective therapeutics against breast cancer cells. The mechanism of action of salicin is probably through ER, PR and HER2 receptors because it can efficiently bind these receptors with minimum energy required for binding. This explains that salicin can easily bind to these receptors. These results together opine that salicin can be an effective therapeutics against breast cancer cells. The mechanism of action of salicin is probably through ER, PR and HER2 receptors because it can efficiently bind these receptors with minimum binding energy. ER, PR and HER2 are major reasons behind the disease pathogenicity depending on the type of breast cancer. According to our results salicin may either induce apoptosis or reduce cellular mitosis both via P53 dependent and independent pathway, which makes salicin a good choice of both hormone positive and negative breast cancer cells. 

Design, synthesis, and anti-proliferative evaluation of 1H-1,2,3-triazole grafted tetrahydro-β-carboline-chalcone/ferrocenylchalcone conjugates in estrogen responsive and triple negative breast cancer cells

2020 ◽  
Vol 44 (26) ◽  
pp. 11137-11147 ◽  
Author(s):  
Bharvi Sharma ◽  
Liang Gu ◽  
Ruvesh Pascal Pillay ◽  
Nosipho Cele ◽  
Paul Awolade ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Cells ◽  
Triple Negative Breast Cancer ◽  
Breast Cancer Cells ◽  
Triple Negative ◽  
Design Synthesis ◽  
Mcf 7

A series of 1H-1,2,3 triazole grafted tetrahydro-β-carboline-chalcone/ferrocenylchalcone conjugates were synthesized and in vitro evaluated against estrogen responsive (MCF-7) and triple negative (MDA-MB-231) breast cancer cells.

scholarly journals NLRP3 as Putative Marker of Ipilimumab-Induced Cardiotoxicity in the Presence of Hyperglycemia in Estrogen-Responsive and Triple-Negative Breast Cancer Cells

2020 ◽  
Vol 21 (20) ◽  
pp. 7802 ◽  
Author(s):  
Vincenzo Quagliariello ◽  
Michelino De Laurentiis ◽  
Stefania Cocco ◽  
Giuseppina Rea ◽  
Annamaria Bonelli ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Cells ◽  
Cell Lines ◽  
Triple Negative Breast Cancer ◽  
High Glucose ◽  
Breast Cancer Cells ◽  
Triple Negative ◽  
Anticancer Efficacy ◽  
Low Glucose ◽  
Mcf 7

Hyperglycemia, obesity and metabolic syndrome are negative prognostic factors in breast cancer patients. Immune checkpoint inhibitors (ICIs) have revolutionized cancer treatment, achieving unprecedented efficacy in multiple malignancies. However, ICIs are associated with immune-related adverse events involving cardiotoxicity. We aimed to study if hyperglycemia could affect ipilimumab-induced anticancer efficacy and enhance its cardiotoxicity. Human cardiomyocytes and estrogen-responsive and triple-negative breast cancer cells (MCF-7 and MDA-MB-231 cell lines) were exposed to ipilimumab under high glucose (25 mM); low glucose (5.5 mM); high glucose and co-administration of SGLT-2 inhibitor (empagliflozin); shifting from high glucose to low glucose. Study of cell viability and the expression of new putative biomarkers of cardiotoxicity and resistance to ICIs (NLRP3, MyD88, cytokines) were quantified through ELISA (Cayman Chemical) methods. Hyperglycemia during treatment with ipilimumab increased cardiotoxicity and reduced mortality of breast cancer cells in a manner that is sensitive to NLRP3. Notably, treatment with ipilimumab and empagliflozin under high glucose or shifting from high glucose to low glucose reduced significantly the magnitude of the effects, increasing responsiveness to ipilimumab and reducing cardiotoxicity. To our knowledge, this is the first evidence that hyperglycemia exacerbates ipilimumab-induced cardiotoxicity and decreases its anticancer efficacy in MCF-7 and MDA-MB-231 cells. This study sets the stage for further tests on other breast cancer cell lines and primary cardiomyocytes and for preclinical trials in mice aimed to decrease glucose through nutritional interventions or administration of gliflozines during treatment with ipilimumab.

scholarly journals Novel Melatonin, Estrogen, and Progesterone Hormone Therapy Demonstrates Anti-Cancer Actions in MCF-7 and MDA-MB-231 Breast Cancer Cells

2020 ◽  
Vol 14 ◽  
pp. 117822342092463
Author(s):  
Mahmud Hasan ◽  
Erin Browne ◽  
Laura Guarinoni ◽  
Travis Darveau ◽  
Katherine Hilton ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Hormone Therapy ◽  
Cancer Cells ◽  
Triple Negative Breast Cancer ◽  
Breast Cancer Cells ◽  
Triple Negative ◽  
Anti Cancer ◽  
And Migration ◽  
Mcf 7 ◽  
Proliferation And Migration

A novel melatonin, estrogen, and progesterone hormone therapy was developed as a safe bio-identical alternative hormone therapy for menopausal women based on the Women’s Health Initiative findings that PremPro™ increased breast cancer risk and mortality of all types of breast cancer in postmenopausal women. For HER2 breast cancer, melatonin, estrogen, and progesterone delayed tumor onset and reduced tumor incidence in neu female mice. For other breast cancers, its actions are unknown. In this study, melatonin, estrogen, and progesterone hormone therapy were assessed in human ER+ (MCF-7) and triple negative breast cancer (MDA-MB-231) cells, and found to decrease proliferation and migration of both breast cancer lines. Inhibition of MEK1/2 and 5 using PD98059 and BIX02189, respectively, inhibited proliferation and migration in MDA-MB-231 cells and proliferation in MCF-7 cells; however, when combined with melatonin, estrogen, and progesterone, BIX02189 blocked melatonin, estrogen, and progesterone–mediated inhibition of migration in MCF-7 cells and induced Elf-5. For MDA-MB-231 cells, BIX02189 combined with melatonin, estrogen, and progesterone inhibited proliferation and increased pERK1/2 and β1-INTEGRIN; levels of pERK5 remained low/nearly absent in both breast cancer lines. These findings demonstrate novel anti-cancer actions of melatonin, estrogen, and progesterone in ER+ and triple negative breast cancer cells through intricate MEK1/2- and MEK5-associated signaling cascades that favor anti-proliferation and anti-migration.

scholarly journals Cytotoxic and radiosensitising effects of a novel thioredoxin reductase inhibitor in breast cancer

2021 ◽  
Author(s):  
Nurul A Abdullah ◽  
Martyn Inman ◽  
Christopher J. Moody ◽  
Sarah J Storr ◽  
Stewart G Martin
Keyword(s):  
Breast Cancer ◽  
Clinical Trial ◽  
Cancer Cells ◽  
Triple Negative Breast Cancer ◽  
Breast Cancer Cells ◽  
Triple Negative ◽  
Reductase Activity ◽  
Thioredoxin Reductase ◽  
Breast Cancer Cell Lines ◽  
Cancer Models

SummaryRadiotherapy is an effective treatment modality for breast cancer but, unfortunately, not all patients respond fully with a significant number experiencing local recurrences. Overexpression of thioredoxin and thioredoxin reductase has been reported to cause multidrug and radiation resistance - their inhibition may therefore improve therapeutic efficacy. Novel indolequinone compounds have been shown, in pancreatic cancer models, to inhibit thioredoxin reductase activity and exhibit potent anticancer activity. The present study evaluates, using in vitro breast cancer models, the efficacy of a novel indolequinone compound (IQ9) as a single agent and in combination with ionising radiation using a variety of endpoint assays including cell proliferation, clonogenic survival, enzyme activity, and western blotting. Three triple-negative breast cancer (MDA-MB-231, MDA-MB-468, and MDA-MB-436) and two luminal (MCF-7 and T47D) breast cancer cell lines were used. Results show that treatment with IQ9 significantly inhibited thioredoxin reductase activity, and inhibited cell growth and colony formation of breast cancer cells with IC50 values in the low micromolar ranges. Enhanced radiosensitivity of triple-negative breast cancer cells was observed, with sensitiser enhancement ratios of 1.20–1.43, but with no evident radiosensitisation of luminal breast cancer cell lines. IQ9 upregulated protein expression of thioredoxin reductase in luminal but not in triple-negative breast cancer cells which may explain the observed differential radiosensitisation. This study provides important evidence of the roles of the thioredoxin system as an exploitable radiobiological target in breast cancer cells and highlights the potential therapeutic value of indolequinones as radiosensitisers.***This study was not part of a clinical trial. Clinical trial registration number: N/A

scholarly journals DFF40-iRGD, As A Novel Chimeric Protein With Efficient Cytotoxic and Apoptotic Effects Against Triple-Negative Breast Cancer Cells

2021 ◽  
Author(s):  
Raheleh Amrollahi-nia ◽  
Vajihe Akbari ◽  
Fatemeh Shafiee
Keyword(s):  
Breast Cancer ◽  
Cancer Cells ◽  
Cell Lines ◽  
Triple Negative Breast Cancer ◽  
Breast Cancer Cells ◽  
Triple Negative ◽  
Soluble Expression ◽  
Soluble Form ◽  
Apoptotic Effects ◽  
Mcf 7

Abstract Purpose DNA fragmenting factor (DFF40), an endonuclease inducing irreversible apoptosis protein, is down-regulated in many types of tumor cells. iRGD is a tumor-penetrating peptide with high affinity to cancer cells overexpressing αVβ3 receptors. The aim of this study was to produce the recombinant DFF40-iRGD protein as a new molecule to selectively induce cytotoxicity in cancer cells and to evaluate its biological effects. Methods The three-dimensional structure of DFF40-iRGD was predicted using Modeller software and its interaction with αVβ3 receptor was evaluated by HADDOCK web-server. Recombinant DFF40 and DFF40-iRGD proteins were produced using intein fusion system in Escherichia coli BL21 (DE3). To improve the soluble expression, the inducer concentration, temperature and incubation time were optimized. After purification of DFF40 and DFF40-iRGD using chitin column, the cytotoxic and apoptotic effects of the proteins against MDA-MB-231 (αVβ3 positive) and MCF-7 (αVβ3 negative) cell lines were evaluated using cell viability assay and flow cytometric analysis. Results The results of molecular docking indicated the proper interaction of DFF40-iRGD with the integrin receptor comparable to iRGD. The optimum conditions of soluble expression of proteins were the induction with 0.5 mM and 0.1 mM of IPTG for DFF40 and DFF40-iRGD, respectively, at 7 ºC for 24 hours. After 48 hours of incubation, DFF40-iRGD exhibited significantly higher cytotoxic effect against MDA-MB-231 cells than MCF-7 cells as IC50 values of 0.77 and 1.64 µg/ml were found for MDA-MB-231 and MCF-7 cells, respectively. However, DFF40 cytotoxicity was not significantly different in two cell lines. Furthermore, Flow cytometry results showed that the fusion protein can induce remarkably apoptotic cell death in cancer cells. Conclusion in this study, DFF40-iRGD protein was produced in soluble form and its inhibitory effects on cancer cell survival and induction of apoptosis were demonstrated; therefore, it has the potential to be used as a drug candidate for targeted treatment of breast cancer, especially Triple Negative Breast Cancer Cells.

scholarly journals Hyperglycemic Conditions Proliferate Triple Negative Breast Cancer Cells: Role of Ornithine Decarboxylase

2021 ◽  
Author(s):  
Surabhi Chandra ◽  
Caleb C. Capellen ◽  
Jose A. Ortega ◽  
M. Jane Morwitzer ◽  
Hadassha Tofilau ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Epithelial Cells ◽  
Cancer Cells ◽  
Ornithine Decarboxylase ◽  
Triple Negative Breast Cancer ◽  
Breast Cancer Cells ◽  
Triple Negative ◽  
Polyamine Synthesis ◽  
Mcf 7

Abstract Several cancer subtypes (pancreatic, breast, liver, and colorectal) rapidly advance to higher aggressive stages in diabetes. Though hyperglycemia has been considered as a fuel for growth of cancer cells, pathways leading to this condition are still under investigation. Cellular polyamines can modulate normal and cancer cell growth, and inhibitors of polyamine synthesis have been approved for treating colon cancer, however the role of polyamines in diabetes-mediated cancer advancement is unclear as yet. We hypothesized that polyamine metabolic pathway is involved with increased proliferation of breast cancer cells under high glucose(HG) conditions. Studies were performed with varying concentrations of glucose (5mM-25mM) exposure in invasive, triple negative breast cancer cells, MDA-MB-231; non-invasive, estrogen/progesterone receptor positive breast cancer cells, MCF-7; and non-tumorigenic mammary epithelial cells, MCF-10A. There was a significant increase in proliferation with HG (25mM) at 48-72h in both MDA-MB-231 and MCF-10A cells but no such effect was observed in MCF-7 cells. This was correlated to higher activity of ornithine decarboxylase (ODC), the rate limiting enzyme in polyamine synthesis pathway. Inhibitor of polyamine synthesis (difluoromethylornithine, DFMO, 5mM) was quite effective in suppressing HG-mediated cell proliferation and ODC activity in MDA-MB-231 and MCF-10A cells. Polyamine (putrescine) levels were significantly elevated with HG treatment in MDA-MB-231 cells. HG exposure also increased the metastasis of MDA-MB-231 cells. Our findings are the first to indicate that polyamine inhibition can improve prognosis of breast cancer patients with diabetes, and also prevent proliferation of normal breast epithelial cells, which could potentially become tumorigenic.

scholarly journals Effects of SAHA and EGCG on Growth Potentiation of Triple-Negative Breast Cancer Cells

Cancers ◽  
2018 ◽  
Vol 11 (1) ◽  
pp. 23 ◽  
Author(s):  
Kayla Lewis ◽  
Harrison Jordan ◽  
Trygve Tollefsbol
Keyword(s):  
Breast Cancer ◽  
Cancer Cells ◽  
Triple Negative Breast Cancer ◽  
Breast Cancer Cells ◽  
White Women ◽  
Triple Negative ◽  
The United States ◽  
Growth Potential ◽  
Breast Cancer Cell Lines

Triple-negative breast cancer comprises approximately 15–20% of all breast cancers diagnosed and is nearly twice as common in black women than white women in the United States. We evaluated the effects of two epigenetic-modifying compounds on markers of growth potential in several triple-negative breast cancer cell lines. Suberoylanilide hydroxamic acid (SAHA), a histone deacetylase (HDAC) inhibitor currently used in the treatment of cutaneous T cell lymphoma, was administered to triple-negative breast cancer cells alone or in combination with epigallocatechin-3-gallate (EGCG), a DNA methyltransferase (DNMT) inhibitor isolated from green tea. The compounds affected the expression of oncogenic miR-221/222 and tumor suppressors, p27 and PTEN, in addition to estrogen receptor alpha (ERα). E-cadherin expression was increased while N-cadherin was decreased, indicating a more epithelial phenotype. In addition, the activity of DNMTs was diminished with the treatments, and there was a significant enrichment of AcH3 within the promoter of p27 and PTEN, suggesting a role of epigenetic mechanisms for the aforementioned changes. These results translated to reduced migration of the triple-negative breast cancer cells with the treatments. Together, these findings support the role of SAHA and EGCG in limiting growth and proliferation of breast cancer cells.

scholarly journals Interplay between Epigenetics, Expression of Estrogen Receptor- α, HER2/ERBB2 and Sensitivity of Triple Negative Breast Cancer Cells to Hormonal Therapy

Cancers ◽  
2018 ◽  
Vol 11 (1) ◽  
pp. 13 ◽  
Author(s):  
Wafaa S Ramadan ◽  
Cijo George Vazhappilly ◽  
Ekram M Saleh ◽  
Varsha Menon ◽  
Aya M. AlAzawi ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Cells ◽  
Triple Negative Breast Cancer ◽  
Hormonal Therapy ◽  
Breast Cancer Cells ◽  
Triple Negative ◽  
Breast Cancer Cell Lines ◽  
Pronounced Increase ◽  
Epigenetic Markers ◽  
Epigenetic Modifiers

Triple negative breast cancer (TNBC) cells are resistant to hormonal/targeted therapies. This study aims to investigate epigenetic differences between TNBC and other types of breast cancer and the effect of epigenetic modulation on the response of TNBC cells to hormonal therapy. Thus, we investigated (i) the expression of different epigenetic markers, (ii) the effect of epigenetic modifying agents on the expression of ERα and HER2/ERBB2 and (iii) the effect on the response to tamoxifen in four breast cancer cell lines with different hormonal receptor status. Our results revealed a differential expression patterns of epigenetic markers in the four breast cancer cells. In TNBC cells, histone deacetylases (HDAC) 1 and 2 were less expressed, whereas HDACs 4 and 6 were overexpressed. Interestingly, treatment with epigenetic modifiers resulted in (i) a pronounced increase in the expression of ERα and HER2/ERBB2 along with (ii) an increase in the sensitivity of TNBC cells to tamoxifen. Collectively, this study indicates a different epigenetic background for TNBC cells, which represses the expression of ERα and HER2/ERBB2. Furthermore, we provide here the rationale for the use of epigenetic modifiers to enhance the response of TNBC to hormonal therapy through upregulation of ERα.

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