Amino-bisphosphonates decrease hTERT gene expression in breast cancer in vitro

Background: : Current drugs used for the treatment of hormone-dependent breast cancer function as anti-estrogens in the breast, in addition to Estrogen Receptor (ER) agonists in the uterus, thus elevate a woman’s risk of developing uterine cancer. This is due to the lack of selective binding and partial agonistic effect of these drugs towards estrogen receptors. In recent years, therefore, researchers have turned their attention towards antiestrogens devoid of these agonist properties and thus have a mechanism of action different from the existing drugs. Objective:: In this context, we report here the design, development and in vitro evaluation of some novel pharmacophores containing coumarin and fatty acid scaffolds for their anti-breast cancer activity. Methods: : A library of coumarin-fatty acid conjugates was designed using structure-based drug design approach. The conjugates which have shown good in silico results were then synthesized, characterized and evaluated for their anti-breast cancer activity by MTT assay, Apoptotic assay, Cell proliferation assay, Estrogen binding assay and Gene expression study. Results: Out of the fifteen compounds screened, two compounds, SAC-2 and LNAC-2, showed good activity with IC50 values 22µg/ml, 25μg/ml, respectively. These compounds suppressed the proliferation of ER overexpressed MCF-7 cells, increased ERα degradation and hence inactivate the ERα pathway. ER binding assay and gene expression RT-PCR study reveal that SAC-2 downregulated the expression of ERα receptor and AKT-1 gene. Conclusion:: Compound SAC-2 is a good antagonist to ER and hence has a potential for treating breast cancer and other cancers where AKT plays an important role.

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CBP/β-Catenin/FOXM1 Is a Novel Therapeutic Target in Triple Negative Breast Cancer

Cancers ◽

10.3390/cancers10120525 ◽

2018 ◽

Vol 10 (12) ◽

pp. 525 ◽

Cited By ~ 9

Author(s):

Alexander Ring ◽

Cu Nguyen ◽

Goar Smbatyan ◽

Debu Tripathy ◽

Min Yu ◽

...

Keyword(s):

Breast Cancer ◽

Gene Expression ◽

Drug Resistance ◽

Triple Negative Breast Cancer ◽

Therapeutic Target ◽

Triple Negative ◽

Creb Binding Protein ◽

Novel Therapeutic

Background: Triple negative breast cancers (TNBCs) are an aggressive BC subtype, characterized by high rates of drug resistance and a high proportion of cancer stem cells (CSC). CSCs are thought to be responsible for tumor initiation and drug resistance. cAMP-response element-binding (CREB) binding protein (CREBBP or CBP) has been implicated in CSC biology and may provide a novel therapeutic target in TNBC. Methods: RNA Seq pre- and post treatment with the CBP-binding small molecule ICG-001 was used to characterize CBP-driven gene expression in TNBC cells. In vitro and in vivo TNBC models were used to determine the therapeutic effect of CBP inhibition via ICG-001. Tissue microarrays (TMAs) were used to investigate the potential of CBP and associated proteins as biomarkers in TNBC. Results: The CBP/ß-catenin/FOXM1 transcriptional complex drives gene expression in TNBC and is associated with increased CSC numbers, drug resistance and poor survival outcome. Targeting of CBP/β-catenin/FOXM1 with ICG-001 eliminated CSCs and sensitized TNBC tumors to chemotherapy. Immunohistochemistry of TMAs demonstrated a significant correlation between FOXM1 expression and TNBC subtype. Conclusion: CBP/β-catenin/FOXM1 transcriptional activity plays an important role in TNBC drug resistance and CSC phenotype. CBP/β-catenin/FOXM1 provides a molecular target for precision therapy in triple negative breast cancer and could form a rationale for potential clinical trials.

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Anti-proliferative and gene expression actions of resveratrol in breast cancer cells in vitro

Oncotarget ◽

10.18632/oncotarget.2632 ◽

2014 ◽

Vol 5 (24) ◽

pp. 12891-12907 ◽

Cited By ~ 44

Author(s):

Yu-Tang Chin ◽

Meng-Ti Hsieh ◽

Sheng-Huei Yang ◽

Po-Wei Tsai ◽

Shwu-Huey Wang ◽

...

Keyword(s):

Breast Cancer ◽

Gene Expression ◽

Cancer Cells ◽

Breast Cancer Cells

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Effect of Auraptene on angiogenesis in Xenograft model of breast cancer

Hormone Molecular Biology and Clinical Investigation ◽

10.1515/hmbci-2021-0056 ◽

2021 ◽

Vol 0 (0) ◽

Author(s):

Mohammad Reza Shiran ◽

Elham Mahmoudian ◽

Abolghasem Ajami ◽

Seyed Mostafa Hosseini ◽

Ayjamal Khojasteh ◽

...

Keyword(s):

Breast Cancer ◽

Gene Expression ◽

Animal Model ◽

Protein Expression ◽

Western Blot ◽

Xenograft Model ◽

Dependent Manner ◽

Concentration Dependent Manner

Abstract Objectives Angiogenesis is the most important challenge in breast cancer treatment. Recently, scientists become interesting in rare natural products and intensive researches was performed to identify their pharmacological profile. Auraptene shows helpful effects such as cancer chemo-preventive, anti-inflammatory, anti-oxidant, immuno-modulatory. In this regard, we investigated the anti-angiogenesis effect of Auraptene in in-vitro and in-vivo model of breast cancer. Methods In this study, 4T, MDA-MB-231 and HUVEC cell lines were used. The proliferation study was done by MTT assay. For tube formation assay, 250 matrigel, 1 × 104 HUVEC treated with Auraptene, 20 ng/mL EGF, 20 ng/mL bFGF and 20 ng/mL VEGF were used. Gene expression of important gene related to angiogenesis in animal model of breast cancer was investigated by Real-time PCR. Protein expression of VCAM-1 and TNFR-1 gene related to angiogenesis in animal model of breast cancer was investigated by western-blot. Results Auraptene treatment led to reduction in cell viability of MDA-MB-231 in a concentration-dependent manner. Also, we observed change in the number of tubes or branches formed by cells incubated with 40 and 80 μM Auraptene. Auraptene effect the gene expression of important gene related to angiogenesis (VEGF, VEGFR2, COX2, IFNɣ). Moreover, the western blot data exhibited that Auraptene effect the protein expression of VCAM-1 and TNFR-1. Conclusions Overall, this study shows that Auraptene significantly suppressed angiogenesis via down-regulation of VEGF, VEGFR2, VCAM-1, TNFR-1, COX-2 and up-regulation of IFNγ.

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Protein arginine methyltransferase 6-dependent gene expression and splicing: association with breast cancer outcomes

Endocrine Related Cancer ◽

10.1530/erc-12-0100 ◽

2012 ◽

Vol 19 (4) ◽

pp. 509-526 ◽

Cited By ~ 16

Author(s):

Dennis H Dowhan ◽

Matthew J Harrison ◽

Natalie A Eriksson ◽

Peter Bailey ◽

Michael A Pearen ◽

...

Keyword(s):

Breast Cancer ◽

Gene Expression ◽

Alternative Splicing ◽

Cancer Cells ◽

Breast Cancer Cells ◽

Gene Expression Signature ◽

Human Breast ◽

Arginine Methyltransferase ◽

Breast Tumours

Protein arginine methyltransferase-6 (PRMT6) regulates steroid-dependent transcription and alternative splicing and is implicated in endocrine system development and function, cell death, cell cycle, gene expression and cancer. Despite its role in these processes, little is known about its function and cellular targets in breast cancer. To identify novel gene targets regulated by PRMT6 in breast cancer cells, we used a combination of small interfering RNA and exon-specific microarray profilingin vitrocoupled toin vivovalidation in normal breast and primary human breast tumours. This approach, which allows the examination of genome-wide changes in individual exon usage and total transcript levels, demonstrated thatPRMT6knockdown significantly affected i) the transcription of 159 genes and ii) alternate splicing of 449 genes. ThePRMT6-dependent transcriptional and alternative splicing targets identifiedin vitrowere validated in human breast tumours. Using the list of genes differentially expressed between normal andPRMT6knockdown cells, we generated aPRMT6-dependent gene expression signature that provides an indication of PRMT6 dysfunction in breast cancer cells. Interrogation of several well-studied breast cancer microarray expression datasets with thePRMT6gene expression signature demonstrated that PRMT6 dysfunction is associated with better overall relapse-free and distant metastasis-free survival in the oestrogen receptor (ER (ESR1)) breast cancer subgroup. These results suggest that dysregulation ofPRMT6-dependent transcription and alternative splicing may be involved in breast cancer pathophysiology and the molecular consequences identifying a unique and informative biomarker profile.

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Lac Repressor Inducible Gene Expression in Human Breast Cancer Cells In Vitro and in a Xenograft Tumor

BioTechniques ◽

10.2144/97236st02 ◽

1997 ◽

Vol 23 (6) ◽

pp. 1062-1068 ◽

Cited By ~ 9

Author(s):

A.V. Lee ◽

C.-N. Weng ◽

S.E. McGuire ◽

D.M. Wolf ◽

D. Yee

Keyword(s):

Breast Cancer ◽

Gene Expression ◽

Human Breast Cancer ◽

Breast Cancer Cells ◽

Lac Repressor ◽

Xenograft Tumor ◽

Human Breast Cancer Cells ◽

Human Breast ◽

Inducible Gene

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Correlation of in vitro lymphocyte radiosensitivity and gene expression with late normal tissue reactions following curative radiotherapy for breast cancer

Breast Diseases A Year Book Quarterly ◽

10.1016/j.breastdis.2013.04.024 ◽

2013 ◽

Vol 24 (2) ◽

pp. 183-184

Author(s):

M.C. Stauder

Keyword(s):

Breast Cancer ◽

Gene Expression ◽

Normal Tissue ◽

Curative Radiotherapy ◽

Tissue Reactions ◽

Normal Tissue Reactions

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Imatinib-induced changes in gene expression and the metastatic potential of human breast carcinoma cells

Journal of Clinical Oncology ◽

10.1200/jco.2009.27.15_suppl.1074 ◽

2009 ◽

Vol 27 (15_suppl) ◽

pp. 1074-1074

Author(s):

A. Lorico ◽

F. Anzanello ◽

G. Rappa

Keyword(s):

Breast Cancer ◽

Gene Expression ◽

Breast Carcinoma ◽

Cancer Cells ◽

Breast Cancer Cells ◽

Carcinoma Cells ◽

Myelogenous Leukemia ◽

Breast Carcinoma Cells

1074 Background: Imatinib mesylate (imatinib) is a potent and selective inhibitor of the tyrosine kinases, Bcr-Abl, c-Kit and platelet-derived growth factor receptors (PDGFRs). Since its advent for the successful treatment of chronic myelogenous leukemia in 2001, the clinical efficacy of imatinib has been investigated in many other human malignancies, including breast cancer. Based on recent reports that chemotherapy selects more invasive and metastasizing cells, we have hypothesized that exposure of breast cancer cells to imatinib could enhance their malignant behavior. Methods: MA-11 breast carcinoma cells, originating from bone marrow micrometastases, were exposed to imatinib in vitro for seven days. After four days of recovery in drug-free medium, biological properties and gene expression pattern were compared with those of the parental cell line. In a separate set of experiments, the effects of in vivo administration of imatinib to athymic nude (nu/nu) mice carrying MA-11 tumors were investigated. Results: In vitro, imatinib treatment increased the motility and invasiveness of the breast cancer cells, and induced over-expression of drug transporters and of a set of genes associated with aggressive and metastatic behavior (Table). In vivo, nu/nu mice subcutaneously implanted with MA-11 cells and treated with nine daily intraperitoneal doses of 60 mg/Kg imatinib developed with greater frequency distant organ metastases vs. control mice implanted with MA-11 and treated with the vehicle alone. Conclusions: Our data caution against the clinical use of imatinib in breast cancer; imatinib-selected breast cancer cells represent an important tool to investigate the pro-metastatic role of differentially expressed genes. [Table: see text] No significant financial relationships to disclose.

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