scholarly journals Valproic acid causes radiosensitivity of breast cancer cells via disrupting the DNA repair pathway

2016 ◽  
Vol 5 (3) ◽  
pp. 859-870 ◽  
Author(s):  
Yue Luo ◽  
Hui Wang ◽  
Xipeng Zhao ◽  
Chao Dong ◽  
Fengmei Zhang ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Valproic Acid ◽  
Dna Repair ◽  
Cancer Cells ◽  
Histone Deacetylase ◽  
Breast Cancer Cells ◽  
Histone Deacetylase Inhibitors ◽  
Clinical Treatment ◽  
Repair Pathway ◽  
Treatment Of Epilepsy

Valproic acid (VPA) is one of the representative compounds of histone deacetylase inhibitors (HDACis) and is used widely for the clinical treatment of epilepsy and other convulsive diseases.

scholarly journals Histone deacetylase inhibitors valproic acid and vorinostat enhance trastuzumab-mediated antibody-dependent cell-mediated phagocytosis

2020 ◽  
Vol 8 (1) ◽  
pp. e000195 ◽  
Author(s):  
Johannes Laengle ◽  
Julijan Kabiljo ◽  
Leah Hunter ◽  
Jakob Homola ◽  
Sophie Prodinger ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Flow Cytometry ◽  
Valproic Acid ◽  
Cancer Cells ◽  
Histone Deacetylase ◽  
Breast Cancer Cells ◽  
Histone Deacetylase Inhibitors ◽  
Combined Treatment ◽  
Dependent Cell ◽  
The Impact

BackgroundThe monoclonal antibody (mAb) trastuzumab is part of the standard of care for patients with human epidermal growth factor receptor 2 (HER2)-overexpressing breast cancer. Antibody-dependent cell-mediated phagocytosis (ADCP) and cytotoxicity (ADCC) are major mechanisms of action of the mAb trastuzumab. Histone deacetylase inhibitors (HDACi), such as valproic acid (VPA) or vorinostat (SAHA), exert several immunostimulatory properties, which contribute at least in part to their anticancer effect. However, the impact of HDACi-induced immunostimulatory effects on trastuzumab-mediated anti-tumor immune response is not well characterized.MethodsWe analyzed the ADCP and ADCC activity of peripheral blood mononuclear cells (PBMCs) from age and gender-matched healthy volunteers (n=5) against HDACi-treated HER2-overexpressing breast cancer cells (SKBR3), using a well-established in vitro three-color imaging flow cytometry and flow cytometry approach.ResultsVPA and SAHA enhanced trastuzumab-mediated ADCP and trastuzumab-independent cytotoxicity. Mechanistically, VPA upregulated the activating antibody-binding receptor Fc-gamma receptor (FcγR) IIA (CD32A) on monocytes (CD14+). Moreover, VPA and SAHA downregulated the anti-apoptotic protein myeloid leukemia cell differentiation 1 (MCL1) in breast cancer cells. Additionally, VPA and SAHA induced an immunogenic cell death, characterized by the exposure of calreticulin (CALR), as well as decreased the “do not eat me” signal CD47 on tumor cells.ConclusionsHDACi VPA and SAHA increase trastuzumab-mediated phagocytosis and trastuzumab-independent cytotoxicity. The immunomodulatory activities of those HDACi support a rationale combined treatment approach with mAb for cancer treatment.

Valproic acid sensitizes breast cancer cells to hydroxyurea through inhibiting RPA2 hyperphosphorylation-mediated DNA repair pathway

DNA Repair ◽  
2017 ◽  
Vol 58 ◽  
pp. 1-12 ◽  
Author(s):  
Youjia Tian ◽  
Guochao Liu ◽  
Hui Wang ◽  
Zhujun Tian ◽  
Zuchao Cai ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Valproic Acid ◽  
Dna Repair ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Repair Pathway

Abstract A55: Histone deacetylase inhibitors as differentiation agents in breast cancer cells

2013 ◽  
Author(s):  
Houssam Ismail ◽  
Martine Bail ◽  
David Laperrière ◽  
Khalid Hilmi ◽  
Sylvie Mader
Keyword(s):  
Breast Cancer ◽  
Cancer Cells ◽  
Histone Deacetylase ◽  
Breast Cancer Cells ◽  
Histone Deacetylase Inhibitors
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