Molecular Mechanisms Underlying the Anti-Breast Cancer Stem Cell Activity of Pterocladia capillacea and Corallina officinalis Polysaccharides

2021 ◽  
Vol 21 ◽  
Author(s):  
Hebatallah G. Hafez ◽  
Rafat M. Mohareb ◽  
Sohair M. Salem ◽  
Azza A. Matloub ◽  
Emad F. Eskander ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Gene Expression ◽  
Signaling Pathways ◽  
Molecular Mechanisms ◽  
Protein Complexes ◽  
Cell Activity ◽  
Sulfated Polysaccharide ◽  
Corallina Officinalis ◽  
Stem Cell Activity ◽  
Mcf 7

Objective: This study aimed to appraise the activity of Pterocladia capillacea and Corallina officinalis polysaccharides against breast cancer stem cells (BCSCs). P. capillacea and C. officinalis polysaccharides were characterized to be sulfated polysaccharide-protein complexes. Methods: Cytotoxicity of the polysaccharides against MDA-MB-231 and MCF-7 cell lines along with their impact on CD44+/CD24− and aldehyde dehydrogenase 1(ALDH1) positive BCSC population were determined. Their effect on gene expression of CSC markers, Wnt/β-catenin and Notch signaling pathways was evaluated. Results: P. capillacea and C. officinalis polysaccharides inhibited the growth of breast cancer cells and reduced BCSC subpopulation. P. capillacea polysaccharides significantly down-regulated OCT4, SOX2, ALDH1A3 and vimentin in MDA-MB-231 as well as in MCF-7 cells except for vimentin that was up-regulated in MCF-7 cells. C. officinalis polysaccharides exhibited similar effects except for OCT4 that was up-regulated in MDA-MB-231 cells. Significant suppression of Cyclin D1 gene expression was noted in MDA-MB-231 and MCF-7 cells treated with P. capillacea or C. officinalis polysaccharides. β-catenin and c-Myc genes were significantly down-regulated in MDA-MB-231 cells treated with C. officinalis and P. capillacea polysaccharides, respectively, while being up-regulated in MCF-7 cells treated with either of them. Additionally, P. capillacea and C. officinalis polysaccharides significantly down-regulated Hes1 gene in MCF-7 cells despite increasing Notch1 gene expression level. However, significant down-regulation of Notch1 gene was observed in MDA-MB-231 cells treated with P. capillacea polysaccharides. Conclusion: Collectively, this study provides evidence for the effectiveness of P. capillacea and C. officinalis polysaccharides in targeting BCSCs through interfering with substantial signaling pathways contributing to their functionality.

scholarly journals Combination of 5-fluorouracil and Lipopolysaccharide Synergistically Induces Cytotoxicity and Apoptosis in MCF-7 Human Breast Cancer Cells

2020 ◽  
Author(s):  
Negin Nokhandani ◽  
Mahdieh Naghavi Alhosseini ◽  
Ali Memarian ◽  
Homa Davoodi
Keyword(s):  
Breast Cancer ◽  
Gene Expression ◽  
Cancer Cells ◽  
Signaling Pathways ◽  
Tumor Cells ◽  
Human Breast Cancer ◽  
Cancer Cell Line ◽  
Human Breast ◽  
Oncology Research ◽  
Mcf 7

Several studies have been conducted to find suitable combinations of drugs to increase the efficacy of chemotherapy and reduce the resistance of tumor cells to treatment. Lipopolysaccharide (LPS), as a ligand for Toll-like receptor 4 (TLR-4), can modify immune responses in different cancers. Although multiple studies have been performed in this area, the effect of LPS on tumor cells remains controversial. In the present study, the cytotoxic effects of 5-fluorouracil (5-FU), with or without LPS, were evaluated in human breast cancer cell line (MCF-7) on apoptosis and gene expression in downstream signaling pathways. MCF-7 was obtained from the Pasteur Institute of Iran. The effects of LPS and 5-FU on cytotoxicity, apoptosis, and gene expression in NF-κB, ERK, and AKT signaling pathways were evaluated by MTT assay, Annexin V/propidium iodide (PI) apoptosis assay, and qRTPCR, respectively. Our findings showed that LPS alone did not significantly affect cytotoxicity or apoptosis, compared to the control cells (untreated cells), while combined with 5-FU, it caused a significant increase in the apoptosis of cancer cells and decreased cell viability. It was also concluded that LPS in combination with 5-FU increased TLR-4 expression and downregulated gene expression in NF-κB, ERK, and AKT pathways (p=0.001). Although the role of LPS in tumor inhibition or progression remains controversial, our findings suggest that LPS can be considered a novel complementary approach intranslational oncology research of breast cancer therapy.

The Expression of Dopamine Receptors Gene and their Potential Role in Targeting Breast Cancer Cells with Selective Agonist and Antagonist Drugs. Could it be the Novel Insight to Therapy?

2019 ◽  
Vol 16 (2) ◽  
pp. 184-197 ◽  
Author(s):  
Hossein Bakhtou ◽  
Asiie Olfatbakhsh ◽  
Abdolkhaegh Deezagi ◽  
Ghasem Ahangari
Keyword(s):  
Breast Cancer ◽  
Gene Expression ◽  
Cancer Cells ◽  
Dopamine Receptors ◽  
Breast Cancer Cells ◽  
D2 Receptors ◽  
Healthy Individuals ◽  
Agonist And Antagonist ◽  
The Mean ◽  
Mcf 7

Background:Breast cancer is one of the common causes of mortality for women in Iran and other parts of the world. The substantial increasing rate of breast cancer in both developed and developing countries warns the scientists to provide more preventive steps and therapeutic measures. This study is conducted to investigate the impact of neurotransmitters (e.g., Dopamine) through their receptors and the importance of cancers via damaging immune system. It also evaluates dopamine receptors gene expression in the women with breast cancer at stages II or III and dopamine receptor D2 (DRD2) related agonist and antagonist drug effects on human breast cancer cells, including MCF-7 and SKBR-3.Methods:The patients were categorized into two groups: 30 native patients who were diagnosed with breast cancer at stages II and III, with the mean age of 44.6 years and they were reported to have the experience of a chronic stress or unpleasant life event. The second group included 30 individuals with the mean age of 39 years as the control group. In order to determine the RNA concentration in all samples, the RNA samples were extracted and cDNA was synthesized. The MCF-7 cells and SKBR-3 cells were treated with dopamine receptors agonists and antagonists. The MTT test was conducted to identify oxidative and reductive enzymes and to specify appropriate dosage at four concentrations of dopamine and Cabergoline on MCF-7 and SKBR-3 cells. Immunofluorescence staining was done by the use of a mixed dye containing acridine orange and ethidiume bromide on account of differentiating between apoptotic and necrotic cells. Flow cytometry assay was an applied method to differentiate necrotic from apoptotic cells.Results:Sixty seven and thirty three percent of the patients were related to stages II and III, respectively. About sixty three percent of the patients expressed ER, while fifty seven percent expressed PR. Thirty seven percent of the patients were identified as HER-2 positive. All types of D2-receptors were expressed in PBMC of patients with breast cancer and healthy individuals. The expression of the whole dopamine receptor subtypes (DRD2-DRD4) was carried out on MCF-7 cell line. The results of RT-PCR confirmed the expression of DRD2 on SKBR-3 cells, whereas the other types of D2- receptors did not have an expression. The remarkable differences in gene expression rates between patients and healthy individuals were revealed in the result of the Real-time PCR analysis. The over expression in DRD2 and DRD4 genes of PBMCs was observed in the patients with breast cancer at stages II and III. The great amount of apoptosis and necrosis occurred after the treatment of MCF-7 cells by Cabergoline from 25 to 100 µmolL-1 concentrations.Conclusion:This study revealed the features of dopamine receptors associated with apoptosis induction in breast cancer cells. Moreover, the use of D2-agonist based on dopamine receptors expression in various breast tumoral cells could be promising as a new insight of complementary therapy in breast cancer.

scholarly journals Comparison of SYK Signaling Networks Reveals the Potential Molecular Determinants of Its Tumor-Promoting and Suppressing Functions

Biomolecules ◽  
2021 ◽  
Vol 11 (2) ◽  
pp. 308
Author(s):  
Marion Buffard ◽  
Aurélien Naldi ◽  
Gilles Freiss ◽  
Marcel Deckert ◽  
Ovidiu Radulescu ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Tumor Suppressor ◽  
Signaling Pathways ◽  
Burkitt Lymphoma ◽  
Molecular Mechanisms ◽  
Signal Propagation ◽  
Tumor Formation ◽  
Tissue Type ◽  
Signaling Networks ◽  
Proteomic Profiling

Spleen tyrosine kinase (SYK) can behave as an oncogene or a tumor suppressor, depending on the cell and tissue type. As pharmacological SYK inhibitors are currently evaluated in clinical trials, it is important to gain more information on the molecular mechanisms underpinning these opposite roles. To this aim, we reconstructed and compared its signaling networks using phosphoproteomic data from breast cancer and Burkitt lymphoma cell lines where SYK behaves as a tumor suppressor and promoter. Bioinformatic analyses allowed for unveiling the main differences in signaling pathways, network topology and signal propagation from SYK to its potential effectors. In breast cancer cells, the SYK target-enriched signaling pathways included intercellular adhesion and Hippo signaling components that are often linked to tumor suppression. In Burkitt lymphoma cells, the SYK target-enriched signaling pathways included molecules that could play a role in SYK pro-oncogenic function in B-cell lymphomas. Several protein interactions were profoundly rewired in the breast cancer network compared with the Burkitt lymphoma network. These data demonstrate that proteomic profiling combined with mathematical network modeling allows untangling complex pathway interplays and revealing difficult to discern interactions among the SYK pathways that positively and negatively affect tumor formation and progression.

MO262THE SINGLE-CELL TRANSCRIPTOMICS OF HUMAN IGA NEPHROPATHY

2021 ◽  
Vol 36 (Supplement_1) ◽  
Author(s):  
Yong Zhong ◽  
Xiangcheng Xiao
Keyword(s):  
Gene Expression ◽  
Single Cell ◽  
Signaling Pathways ◽  
Iga Nephropathy ◽  
Molecular Mechanisms ◽  
Mesangial Cells ◽  
Therapeutic Targets ◽  
Cell Types ◽  
Receptor Crosstalk ◽  
Overt Proteinuria

Abstract Background and Aims The exact molecular mechanisms underlying IgA nephropathy (IgAN) remains incompletely defined. Therefore, it is necessary to further elucidate the mechanism of IgA nephropathy and find novel therapeutic targets. Method Single-cell RNA sequencing (scRNA-seq) was applied to kidney biopsies from 4 IgAN and 1 control subjects to define the transcriptomic landscape at the single-cell resolution. Unsupervised clustering analysis of kidney specimens was used to identify distinct cell clusters. Differentially expressed genes and potential signaling pathways involved in IgAN were also identified. Results Our analysis identified 14 cell subsets in kidney biopsies from IgAN patients, and analyzed changing gene expression in distinct renal cell types. We found increased mesangial expression of several novel genes including MALAT1, GADD45B, SOX4 and EDIL3, which were related to proliferation and matrix accumulation and have not been reported in IgAN previously. The overexpressed genes in tubule cells of IgAN were mainly enriched in inflammatory pathways including TNF signaling, IL-17 signaling and NOD-like receptor signaling. Moreover, the receptor-ligand crosstalk analysis revealed potential interactions between mesangial cells and other cells in IgAN. Specifically, IgAN with overt proteinuria displayed elevated genes participating in several signaling pathways which may be involved in pathogenesis of progression of IgAN. Conclusion The comprehensive analysis of kidney biopsy specimen demonstrated different gene expression profile, potential pathologic ligand-receptor crosstalk, signaling pathways in human IgAN. These results offer new insight into pathogenesis and identify new therapeutic targets for patients with IgA nephropathy.

The palladacycle, AJ-5, exhibits anti-tumour and anti-cancer stem cell activity in breast cancer cells

2015 ◽  
Vol 357 (1) ◽  
pp. 206-218 ◽  
Author(s):  
Saeb Aliwaini ◽  
Jade Peres ◽  
Wendy L. Kröger ◽  
Angelique Blanckenberg ◽  
Jo de la Mare ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Stem Cell ◽  
Cancer Stem Cell ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Cell Activity ◽  
Anti Cancer ◽  
Stem Cell Activity
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