scholarly journals Citrus sinensis (L) Peels Extract Inhibits Metastasis of Breast Cancer Cells by Targeting the Downregulation Matrix Metalloproteinases-9

2021 ◽  
Vol 9 (B) ◽  
pp. 464-469
Author(s):  
Meiny Suzery ◽  
Bambang Cahyono ◽  
Nur Dina Amalina
Keyword(s):  
Breast Cancer ◽  
Molecular Docking ◽  
Cancer Cells ◽  
Mtt Assay ◽  
Side Effect ◽  
Citrus Sinensis ◽  
Breast Cancer Cells ◽  
Metastatic Breast ◽  
Metastatic Potential ◽  
Matrix Metalloproteinases 9

Introduction: Long-term use of doxorubicin (DOX) chemotherapy causes several side effects, especially induction of metastasis on breast cancer (BC). There is an urgent need to identify novel agent with low side effect targeting BC metastasis. Citrus sinensis (L.) peels extract (CSP) has long been used for the treatment of several cancer. However, its anti-metastatic potential against BC metastatic remains unclear. Objective: This study aimed to explore the role of CSP in combination with DOX in inhibiting the migration of metastatic breast cancer MDAMB-231 cells. Material and Methods: Potential cytotoxic in single and combination was analysed 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay (MTT assay). The anti-metastatic activities of several major compound on CSP including hesperetin, tangeretin, nobiletin, naringenin and hesperidin were screened by molecular docking under PLANTS software. Results: Based on molecular docking we revealed that the selected protein target MMP-9 (PBD ID:2OVX) has lower docking score for hesperetin, tangeretin, nobiletin, naringenin and hesperidin compare to DOX. CSP and DOX individually exhibited strong cytotoxic effect on MDA-MB-231 cells under MTT assay with IC50 value of 344 µg/mL and 85 nM, respectively. Furthermore, CSP in combination with DOX synergistically increased the cytotoxicity of DOX. Here, we showed that CSP can specifically suppress the side effect of DOX-induced metastasis by reduces doses of DOX. However, low doses of DOX in combination with CSP still potential inhibited cancer cells growth. Conclusion: In conclusion, CSP increased the cytotoxicity and inhibited the induction of metastasis by DOX in breast cancer cells. So that, CSP potential to be developed as co-chemotherapeutic agent.

Quartz crystal microbalance based biosensors for detecting highly metastatic breast cancer cells via their transferrin receptors

2016 ◽  
Vol 8 (1) ◽  
pp. 153-161 ◽  
Author(s):  
Seda Atay ◽  
Kevser Pişkin ◽  
Fatma Yılmaz ◽  
Canan Çakır ◽  
Handan Yavuz ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Quartz Crystal ◽  
Metastatic Breast ◽  
High Sensitivity ◽  
Breast Cancer Diagnosis ◽  
Metastatic Potential ◽  
Efficient System ◽  
Ligand Interactions

The high sensitivity of the QCM sensor is combined with selectivity of receptor–ligand interactions to construct a biosensor which would discriminate breast cancer cells with high metastatic power from those of low or no metastatic potential to develop a simple, fast and efficient system to be used in breast cancer diagnosis.

scholarly journals Cancer-associated Fibroblasts Release Exosomal CBFB That Dictate an Aggressive Bone Metastasis Phenotype in Breast Cancer 

2020 ◽  
Author(s):  
Chih Ming Su ◽  
Wen-Chien Huang ◽  
Kuang-Tai Kuo ◽  
Ming-Shou Hsieh ◽  
Iat-Hang Fong ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Bone Metastasis ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Therapeutic Potential ◽  
Standard Procedure ◽  
Metastatic Breast ◽  
Metastatic Potential ◽  
Breast Cancer Cell Lines

Abstract Background: Breast cancer up to date remains the one of the most prevalent female malignancies in the world. Better prognostic and therapeutic biomarkers are urgently required for these patients. Circulating exosomes are shown to participate in tumorigenesis including distance metastasis and of prognostic/therapeutic potential. Methods: Sera from control health, primary breast cancer, and bone metastatic breast cancer patients were collected. The Exosome were isolated from collected sera and culture medium from previously steps, and a standard procedure was performed. We utilized MDA-MB-436-derived xenograft mouse model to demonstrate that silencing CBFB (core binding factor subunit β) significantly reduced bone-metastasis in association with reduced expression of OPN, IL-6, Runx2 and OPN as well as reduced exosomes containing CBFB.Results: We found that circulating exosomes (Exos), from bone metastatic patients with breast cancer, were enriched with CBFB. Fibroblasts co-cultured with Exos showed increased α-SMA, vimentin expression and increased secretion of IL-6 and OPN; non-metastatic breast cancer cells co-cultured with Exos exhibited increased markers including vimentin, snail1, CXCR4 and Runx2. Subsequent analysis revealed that these Exos were enriched with bone metastasis associated maker CBFB. Gene-silencing experiments metastatic MDA-MB-436 and MDA-MB-157 cells, demonstrated that CBFB significantly reduced metastatic potential, reflected by the suppression of vimentin, CXCR4, snail1 and Runx2, CD44 and OPN. In contrary, CBFB-overexpression resulted in the increased metastasis associated genes in non-metastatic T47D and MCF7 cells. The CBFB-enriched exosomes derived from MDA-MB-436 enhanced metastatic phenotypes of low metastatic potential breast cancer cell lines. Conclusion: We demonstrated the essential roles of CBFB in the promotion of bone metastasis in breast cancer cells. The suppression of CBFB led to the decreased tumor burden and bone metastasis in association with decreased markers of bone metastasis including CXCR4, Snail, CD44, OPN, Runx2 and IL-6.

scholarly journals Cancer-Associated Fibroblasts Release Exosomal CBFB That Dictate an Aggressive Bone Metastasis Phenotype in Breast Cancer

2020 ◽  
Author(s):  
Chih-Ming Su ◽  
Yu-Hsin Lai ◽  
Oluwaseun Adebayo Bamodu ◽  
Kuang-Tai Kuo ◽  
Iat-Hang Fong ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Bone Metastasis ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Therapeutic Potential ◽  
Standard Procedure ◽  
Metastatic Breast ◽  
Metastatic Potential ◽  
Breast Cancer Cell Lines

Abstract BackgroundBreast cancer up to date remains the one of the most prevalent female malignancies in the world. Better prognostic and therapeutic biomarkers are urgently required for these patients. Circulating exosomes are shown to participate in tumorigenesis including distance metastasis and of prognostic/therapeutic potential. MethodsSera from control health, primary breast cancer, and bone metastatic breast cancer patients were collected. The Exosome were isolated from collected sera and culture medium from previously steps, and a standard procedure was performed. We utilized MDA-MB-436-derived xenograft mouse model to demonstrate that silencing CBFB (core binding factor subunit β) significantly reduced bone-metastasis in association with reduced expression of OPN, IL-6, Runx2 and OPN as well as reduced exosomes containing CBFB.ResultsWe found that circulating exosomes (Exos), from bone metastatic patients with breast cancer, were enriched with CBFB. Fibroblasts co-cultured with Exos showed increased α-SMA, vimentin expression and increased secretion of IL-6 and OPN; non-metastatic breast cancer cells co-cultured with Exos exhibited increased markers including vimentin, snail1, CXCR4 and Runx2. Subsequent analysis revealed that these Exos were enriched with bone metastasis associated maker CBFB. Gene-silencing experiments metastatic MDA-MB-436 and MDA-MB-157 cells, demonstrated that CBFB significantly reduced metastatic potential, reflected by the suppression of vimentin, CXCR4, snail1 and Runx2, CD44 and OPN. In contrary, CBFB-overexpression resulted in the increased metastasis associated genes in non-metastatic T47D and MCF7 cells. The CBFB-enriched exosomes derived from MDA-MB-436 enhanced metastatic phenotypes of low metastatic potential breast cancer cell lines. ConclusionWe demonstrated the essential roles of CBFB in the promotion of bone metastasis in breast cancer cells. The suppression of CBFB led to the decreased tumor burden and bone metastasis in association with decreased markers of bone metastasis including CXCR4, Snail, CD44, OPN, Runx2 and IL-6.

scholarly journals The migration of metastatic breast cancer cells is regulated by matrix stiffness via YAP signalling

Heliyon ◽  
2021 ◽  
Vol 7 (2) ◽  
pp. e06252
Author(s):  
Wei Chen ◽  
Shihyun Park ◽  
Chrishma Patel ◽  
Yuxin Bai ◽  
Karim Henary ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Metastatic Breast ◽  
Matrix Stiffness

750 Malat1 lncRNA controls metastatic reactivation of dormant breast cancer by immune evasion

2020 ◽  
Vol 8 (Suppl 3) ◽  
pp. A799-A799
Author(s):  
Dhiraj Kumar ◽  
Sreeharsha Gurrapu ◽  
Hyunho Han ◽  
Yan Wang ◽  
Seongyeon Bae ◽  
...  
Keyword(s):  
Breast Cancer ◽  
T Cells ◽  
Single Cell ◽  
Cancer Cells ◽  
Tumor Cells ◽  
Immune Evasion ◽  
Breast Cancer Cells ◽  
Metastatic Potential ◽  
Rna Seq

BackgroundLong non-coding RNAs (lncRNAs) are involved in various biological processes and diseases. Malat1 (metastasis-associated lung adenocarcinoma transcript 1), also known as Neat2, is one of the most abundant and highly conserved nuclear lncRNAs. Several studies have shown that the expression of lncRNA Malat1 is associated with metastasis and serving as a predictive marker for various tumor progression. Metastatic relapse often develops years after primary tumor removal as a result of disseminated tumor cells undergoing a period of latency in the target organ.1–4 However, the correlation of tumor intrinsic lncRNA in regulation of tumor dormancy and immune evasion is largely unknown.MethodsUsing an in vivo screening platform for the isolation of genetic entities involved in either dormancy or reactivation of breast cancer tumor cells, we have identified Malat1 as a positive mediator of metastatic reactivation. To functionally uncover the role of Malat1 in metastatic reactivation, we have developed a knock out (KO) model by using paired gRNA CRISPR-Cas9 deletion approach in metastatic breast and other cancer types, including lung, colon and melanoma. As proof of concept we also used inducible knockdown system under in vivo models. To delineate the immune micro-environment, we have used 10X genomics single cell RNA-seq, ChIRP-seq, multi-color flowcytometry, RNA-FISH and immunofluorescence.ResultsOur results reveal that the deletion of Malat1 abrogates the tumorigenic and metastatic potential of these tumors and supports long-term survival without affecting their ploidy, proliferation, and nuclear speckles formation. In contrast, overexpression of Malat1 leads to metastatic reactivation of dormant breast cancer cells. Moreover, the loss of Malat1 in metastatic cells induces dormancy features and inhibits cancer stemness. Our RNA-seq and ChIRP-seq data indicate that Malat1 KO downregulates several immune evasion and stemness associated genes. Strikingly, Malat1 KO cells exhibit metastatic outgrowth when injected in T cells defective mice. Our single-cell RNA-seq cluster analysis and multi-color flow cytometry data show a greater proportion of T cells and reduce Neutrophils infiltration in KO mice which indicate that the immune microenvironment playing an important role in Malat1-dependent immune evasion. Mechanistically, loss of Malat1 is associated with reduced expression of Serpinb6b, which protects the tumor cells from cytotoxic killing by the T cells. Indeed, overexpression of Serpinb6b rescued the metastatic potential of Malat1 KO cells by protecting against cytotoxic T cells.ConclusionsCollectively, our data indicate that targeting this novel cancer-cell-initiated domino effect within the immune system represents a new strategy to inhibit tumor metastatic reactivation.Trial RegistrationN/AEthics ApprovalFor all the animal studies in the present study, the study protocols were approved by the Institutional Animal Care and Use Committee(IACUC) of UT MD Anderson Cancer Center.ConsentN/AReferencesArun G, Diermeier S, Akerman M, et al., Differentiation of mammary tumors and reduction in metastasis upon Malat1 lncRNA loss. Genes Dev 2016 Jan 1;30(1):34–51.Filippo G. Giancotti, mechanisms governing metastatic dormancy and reactivation. Cell 2013 Nov 7;155(4):750–764.Gao H, Chakraborty G, Lee-Lim AP, et al., The BMP inhibitor Coco reactivates breast cancer cells at lung metastatic sites. Cell 2012b;150:764–779.Gao H, Chakraborty G, Lee-Lim AP, et al., Forward genetic screens in mice uncover mediators and suppressors of metastatic reactivation. Proc Natl Acad Sci U S A 2014 Nov 18; 111(46): 16532–16537.

scholarly journals Comparative effect of thermo/pH-responsive polymer-coated gold nanocages and hollow nanostars on chemo-photothermal therapy of breast cancer cells

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Asrin Pakravan ◽  
Mehdi Azizi ◽  
Fariborz Rahimi ◽  
Farhad Bani ◽  
Farideh Mahmoudzadeh ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Cells ◽  
Mtt Assay ◽  
Photothermal Therapy ◽  
Breast Cancer Cells ◽  
Covalent Attachment ◽  
Mcf7 Cells ◽  
Dapi Staining ◽  
Hemolysis Assay ◽  
Gold Nanocages

Abstract Background Combination chemo-photothermal therapy appears to be one of the next generations of cancer treatment. In this study hollow gold nanostars (HGNSs) and gold nanocages (GNCs) were synthesized and stabilized with thermo-pH-sensitive thiol-end capped ABC triblock copolymer poly(acrylic acid)-b-poly(N isopropylacrylamide)-b-poly (e-caprolactone)-SH; PAA-b-PNIPAAm-b-PCL-SH (GNSs@Pol). Doxorubicin (Dox) was conjugated to the GNSs@Pol nanostructures via ionic interaction, covalent attachment and hydrogen bonding (GNSs@Dox-Pol). The physicochemical characteristics of prepared GNSs@Pol and GNSs were assessed using dynamic light scattering (DLS), transmission electron microscopy (TEM) and zeta potential techniques. Cytocompatibility of the GNSs@Pol was studied by hemolysis assay and MTT assay. The chemo-photothermal therapy (PTT) potential of GNSs@Dox-Pol was compared on MCF7 cells using MTT assay, cell cycle, DAPI staining and Annexin-V apoptosis assay techniques. Results Cell internalization results showed an almost complete uptake of GNSs@Pol by MCF-7 cells in the first 3 h of treatment. The heat generation measurement results showed that both of GNSs have a potential for light to heat conversion (∆T = 23–27 ºC) and HGNSs demonstrated better efficiency than GNCs after 10-min exposure to NIR irradiation. Following chemo-photothermal treatment, the highest cell mortality (90%) and apoptotic effects (97% apoptosis) were observed in HGNSs@Dox-Pol received laser irradiation treatment group. Conclusions This work highlights the potential application of designed GNSs@Dox-Pol in a combinational chemo-PTT to treat breast cancer cells. Graphic abstract

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