scholarly journals HDAC inhibitors stimulate LIFR when it is repressed by hypoxia or PTHrP in breast cancer

2021 ◽  
pp. 100407
Author(s):  
Courtney M. Edwards ◽  
Miranda E. Clements ◽  
Lawrence A. Vecchi ◽  
Jasmine A. Johnson ◽  
Rachelle W. Johnson
Keyword(s):  
Breast Cancer ◽  
Hdac Inhibitors

scholarly journals Biochemical and Anti-Triple Negative Metastatic Breast Tumor Cell Properties of Psammaplins

Marine Drugs ◽  
2018 ◽  
Vol 16 (11) ◽  
pp. 442 ◽  
Author(s):  
Yu-Dong Zhou ◽  
Jun Li ◽  
Lin Du ◽  
Fakhri Mahdi ◽  
Thuy Le ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Tumor Cell ◽  
Tumor Cells ◽  
Breast Tumor ◽  
Triple Negative ◽  
Hdac Inhibitors ◽  
Metastatic Breast ◽  
Dependent Manner ◽  
Breast Tumor Cells ◽  
Metastatic Breast Tumor

Breast tumors reprogram their cellular metabolism, nutrient uptake, and utilization-associated biochemical processes. These processes become further transformed as genetically predisposed metastatic breast tumor cells colonize specific organs. Breast tumor cells often metastasize to the brain, bone, lung and liver. Massagué and colleagues isolated organotropic subclones and established organ-specific gene signatures associated with lung-, bone-, and brain-specific metastatic triple-negative breast cancer (TNBC) MDA-MB-231 cells. Using these genetically characterized metastatic subclones specific to lung (LM4175), bone (BoM1833), and brain (BrM-2a), we evaluated marine natural products for the ability to differentially suppress metastatic breast cancer cells in a target organ-dependent manner. Psammaplin-based histone deacetylase (HDAC) inhibitors were found to differentially inhibit HDAC activity, induce activation of hypoxia-inducible factor-1 (HIF-1), and disrupt organotropic metastatic TNBC subclone growth. Further, psammaplins distinctly suppressed the outgrowth of BoM1833 tumor spheroids in 3D-culture systems. Similar results were observed with the prototypical HDAC inhibitor trichostatin A (TSA). These organotropic tumor cell-based studies suggest the potential application of HDAC inhibitors that may yield new directions for anti-metastatic breast tumor research and drug discovery.

Abstract P3-11-08: Targeting LIFR enhances the activity of HDAC inhibitors for the treatment of triple negative breast cancer

2020 ◽  
Author(s):  
Suryavathi Viswanadhapalli ◽  
Mengxing Li ◽  
Bindu Santhamma ◽  
Uday P Pratap ◽  
Yiliao Luo ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Hdac Inhibitors

scholarly journals Histone deacetylase 11 inhibition promotes breast cancer metastasis from lymph nodes

2019 ◽  
Vol 10 (1) ◽  
Author(s):  
Patrick L. Leslie ◽  
Yvonne L. Chao ◽  
Yi-Hsuan Tsai ◽  
Subrata K. Ghosh ◽  
Alessandro Porrello ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Histone Deacetylase ◽  
Cancer Metastasis ◽  
Hdac Inhibitors ◽  
Distant Metastases ◽  
Breast Cancer Metastasis ◽  
Breast Cancer Patients ◽  
Metastasis Development ◽  
Breast Cancer Growth ◽  
Worse Prognosis

Abstract Lymph node (LN) metastases correspond with a worse prognosis in nearly all cancers, yet the occurrence of cancer spreading from LNs remains controversial. Additionally, the mechanisms explaining how cancers survive and exit LNs are largely unknown. Here, we show that breast cancer patients frequently have LN metastases that closely resemble distant metastases. In addition, using a microsurgical model, we show how LN metastasis development and dissemination is regulated by the expression of a chromatin modifier, histone deacetylase 11 (HDAC11). Genetic and pharmacologic blockade of HDAC11 decreases LN tumor growth, yet substantially increases migration and distant metastasis formation. Collectively, we reveal a mechanism explaining how HDAC11 plasticity promotes breast cancer growth as well as dissemination from LNs and suggest caution with the use of HDAC inhibitors.

Small molecule HDAC inhibitors: Promising agents for breast cancer treatment

2019 ◽  
Vol 91 ◽  
pp. 103184 ◽  
Author(s):  
Meiling Huang ◽  
Jian Zhang ◽  
Changjiao Yan ◽  
Xiaohui Li ◽  
Juliang Zhang ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Treatment ◽  
Small Molecule ◽  
Hdac Inhibitors ◽  
Breast Cancer Treatment

scholarly journals HDAC Inhibitors Target HDAC5, Upregulate MicroRNA-125a-5p, and Induce Apoptosis in Breast Cancer Cells

2015 ◽  
Vol 23 (4) ◽  
pp. 656-666 ◽  
Author(s):  
Tsung-Hua Hsieh ◽  
Chia-Yi Hsu ◽  
Cheng-Fang Tsai ◽  
Cheng-Yu Long ◽  
Chin-Hu Wu ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Hdac Inhibitors

scholarly journals Effect of Trichostatin A on Histone Deacetylases 1, 2 and 3, p21Cip1/Waf1/Sdi1, p27Kip1, and p57Kip2 Gene Expression in Breast Cancer SK-BR-3 Cell Line

2020 ◽  
Vol 5 (2) ◽  
pp. 57-62
Author(s):  
Masumeh Sanaei ◽  
Fraidoon Kavoosi
Keyword(s):  
Breast Cancer ◽  
Gene Expression ◽  
Cell Line ◽  
Cell Apoptosis ◽  
Histone Deacetylases ◽  
Trichostatin A ◽  
Hdac Inhibitors ◽  
Histone Deacetylation ◽  
Relative Expression Level ◽  
Hematological Cancers

Objective: DNA methylation, the covalent addition of a methyl group to cytosine, and histone modification play an important role in the establishment and maintenance of the program of gene expression. The balance of histone acetylation is determined by the activities of two groups of enzymes including histone acetyltransferases (HATs) and histone deacetylases (HDACs). Histone deacetylation is generally associated with silencing gene expression resulting in several solid tumors. HDAC inhibitors (HDACIs) are the new class of potential anticancer compounds for the treatment of the solid and hematological cancers. The current study was designed to evaluate the effect of trichostatin A (TSA) on histone deacetylases 1, 2 and 3, p21Cip1/Waf1/Sdi1 (p21), p27Kip1 (p27), and p57Kip2 (p57) gene expression in breast cancer SK-BR-3 cell line. Materials and Methods: The breast cancer SK-BR-3 line was treated with TSA. To determine cell viability, cell apoptosis, and the relative expression level of the genes, MTT assay, cell apoptosis assay, and qRT-PCR were done respectively. Results: TSA significantly inhibited cell growth, and induced apoptosis. Furthermore, this compound increased p21, p27, and p57 and decreased histone deacetylases 1, 2 and 3 gene expression significantly. Conclusion: The TSA can reactivate the p21, p27, and p57 through down-regulation of histone deacetylases 1, 2 and 3 gene expression.

scholarly journals LIFR inhibition enhances the therapeutic efficacy of HDAC inhibitors in triple negative breast cancer

2021 ◽  
Vol 4 (1) ◽  
Author(s):  
Mengxing Li ◽  
Suryavathi Viswanadhapalli ◽  
Bindu Santhamma ◽  
Uday P. Pratap ◽  
Yiliao Luo ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Triple Negative Breast Cancer ◽  
Therapeutic Efficacy ◽  
Histone Deacetylase Inhibitors ◽  
Triple Negative ◽  
Hdac Inhibitors ◽  
Rna Seq ◽  
Leukemia Inhibitory Factor Receptor ◽  
Targeted Inhibition

AbstractHistone deacetylase inhibitors (HDACi) are identified as novel therapeutic agents, however, recent clinical studies suggested that they are marginally effective in treating triple negative breast cancer (TNBC). Here, we show that first-in-class Leukemia Inhibitory Factor Receptor (LIFRα) inhibitor EC359 could enhance the therapeutic efficacy of HDACi against TNBC. We observed that both targeted knockdown of LIFR with CRISPR or treatment with EC359 enhanced the potency of four different HDACi in reducing cell viability, cell survival, and enhanced apoptosis compared to monotherapy in TNBC cells. RNA-seq studies demonstrated oncogenic/survival signaling pathways activated by HDACi were attenuated by the EC359 + HDACi therapy. Importantly, combination therapy potently inhibited the growth of TNBC patient derived explants, cell derived xenografts and patient-derived xenografts in vivo. Collectively, our results suggest that targeted inhibition of LIFR can enhance the therapeutic efficacy of HDACi in TNBC.

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