scholarly journals Sensitization of MCF7 Cells with High Notch1 Activity by Cisplatin and Histone Deacetylase Inhibitors Applied Together

2021 ◽  
Vol 22 (10) ◽  
pp. 5184
Author(s):  
Anna Wawruszak ◽  
Jarogniew Luszczki ◽  
Marta Halasa ◽  
Estera Okon ◽  
Sebastian Landor ◽  
...  
Keyword(s):  
Histone Deacetylase ◽  
Histone Deacetylase Inhibitors ◽  
Combined Therapy ◽  
Fixed Ratio ◽  
Activity Level ◽  
Mcf7 Cells ◽  
Pharmacological Interaction ◽  
Isobolographic Analysis ◽  
Anti Cancer ◽  
Luminal Type

Histone deacetylase inhibitors (HDIs) are promising anti-cancer agents that inhibit proliferation of many types of cancer cells including breast carcinoma (BC) cells. In the present study, we investigated the influence of the Notch1 activity level on the pharmacological interaction between cisplatin (CDDP) and two HDIs, valproic acid (VPA) and suberoylanilide hydroxamic acid (SAHA, vorinostat), in luminal-like BC cells. The type of drug–drug interaction between CDDP and HDIs was determined by isobolographic analysis. MCF7 cells were genetically modified to express differential levels of Notch1 activity. The cytotoxic effect of SAHA or VPA was higher on cells with decreased Notch1 activity and lower for cells with increased Notch1 activity than native BC cells. The isobolographic analysis demonstrated that combinations of CDDP with SAHA or VPA at a fixed ratio of 1:1 exerted additive or additive with tendency toward synergism interactions. Therefore, treatment of CDDP with HDIs could be used to optimize a combined therapy based on CDDP against Notch1-altered luminal BC. In conclusion, the combined therapy of HDIs and CDDP may be a promising therapeutic tool in the treatment of luminal-type BC with altered Notch1 activity.

scholarly journals Additive Pharmacological Interaction between Cisplatin (CDDP) and Histone Deacetylase Inhibitors (HDIs) in MDA-MB-231 Triple Negative Breast Cancer (TNBC) Cells with Altered Notch1 Activity—An Isobolographic Analysis

2019 ◽  
Vol 20 (15) ◽  
pp. 3663 ◽  
Author(s):  
Anna Wawruszak ◽  
Jarogniew J. Luszczki ◽  
Joanna Kalafut ◽  
Karolina Okla ◽  
Marta Halasa ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Histone Deacetylase ◽  
Triple Negative Breast Cancer ◽  
Histone Deacetylase Inhibitors ◽  
Triple Negative ◽  
Activity Level ◽  
Additive Interaction ◽  
Pharmacological Interaction ◽  
Isobolographic Analysis

The aim of this study was to investigate the influence of the Notch1 activity level on the pharmacological interaction between cisplatin (CDDP) and two histone deacetylase inhibitors (HDIs)—valproic acid (VPA) and vorinostat (SAHA) in the triple negative breast cancer (TNBC) cells. Stable breast cancer (BC) cell lines with increased and decreased activity of Notch1 were generated using a transfection method. The type of interaction between CDDP and the HDIs was determined by isobolographic analysis of cell proliferation in MDA-MB-231 cells with differential levels of Notch1 activity in vitro. The combination of CDDP/SAHA and CDDP/VPA in the MDA-MB-231 triple negative breast cancer (TNBC) cells with increased activity of Notch1, as well as CDDP/VPA in the MDA-MB-231 cells with decreased activity of Notch1, yielded an additive interaction, whereas additivity with a tendency towards antagonism was observed for the combination of CDDP/SAHA in MDA-MB-231 cells with the decreased activity of Notch1. Our studies demonstrated that SAHA and VPA might be considered as potential therapeutic agents in combination therapy with CDDP against TNBC with altered Notch1 activity.

scholarly journals Antagonistic Interaction between Histone Deacetylase Inhibitor: Cambinol and Cisplatin—An Isobolographic Analysis in Breast Cancer In Vitro Models

2021 ◽  
Vol 22 (16) ◽  
pp. 8573
Author(s):  
Marta Hałasa ◽  
Jarogniew J. Łuszczki ◽  
Magdalena Dmoszyńska-Graniczka ◽  
Marzena Baran ◽  
Estera Okoń ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cell Cycle ◽  
Histone Deacetylase ◽  
Cell Lines ◽  
Histone Deacetylase Inhibitor ◽  
Pharmacological Interaction ◽  
Isobolographic Analysis ◽  
Antagonistic Interaction ◽  
Deacetylase Inhibitor ◽  
Anti Cancer

Breast cancer (BC) is the leading cause of death in women all over the world. Currently, combined chemotherapy with two or more agents is considered a promising anti-cancer tool to achieve better therapeutic response and to reduce therapy-related side effects. In our study, we demonstrated an antagonistic effect of cytostatic agent-cisplatin (CDDP) and histone deacetylase inhibitor: cambinol (CAM) for breast cancer cell lines with different phenotypes: estrogen receptor positive (MCF7, T47D) and triple negative (MDA-MB-231, MDA-MB-468). The type of pharmacological interaction was assessed by an isobolographic analysis. Our results showed that both agents used separately induced cell apoptosis; however, applying them in combination ameliorated antiproliferative effect for all BC cell lines indicating antagonistic interaction. Cell cycle analysis showed that CAM abolished cell cycle arrest in S phase, which was induced by CDDP. Additionally, CAM increased cell proliferation compared to CDDP used alone. Our data indicate that CAM and CDDP used in combination produce antagonistic interaction, which could inhibit anti-cancer treatment efficacy, showing importance of preclinical testing.

scholarly journals Histone deacetylase inhibitors: potential targets responsible for their anti-cancer effect

2010 ◽  
Vol 28 (S1) ◽  
pp. 3-20 ◽  
Author(s):  
Michael Dickinson ◽  
Ricky W. Johnstone ◽  
H. Miles Prince
Keyword(s):  
Histone Deacetylase ◽  
Histone Deacetylase Inhibitors ◽  
Anti Cancer

scholarly journals The ROMP: A Powerful Approach to Synthesize Novel pH-Sensitive Nanoparticles for Tumor Therapy

Biomolecules ◽  
2019 ◽  
Vol 9 (2) ◽  
pp. 60 ◽  
Author(s):  
Philippe Bertrand ◽  
Christophe Blanquart ◽  
Valérie Héroguez
Keyword(s):  
Histone Deacetylase ◽  
Histone Deacetylase Inhibitors ◽  
Tumor Therapy ◽  
Systemic Toxicity ◽  
Oxide Shell ◽  
Cancer Drugs ◽  
Native Form ◽  
In Vivo Models ◽  
Anti Cancer

Fast clearance, metabolism, and systemic toxicity are major limits for the clinical use of anti-cancer drugs. Histone deacetylase inhibitors (HDACi) present these defects, despite displaying promising anti-tumor properties on tumor cells in vitro and in in vivo models of cancer. The specific delivery of anti-cancer drugs into the tumor should improve their clinical benefit by limiting systemic toxicity and by increasing the anti-tumor effect. This paper deals with the synthesis of the polymeric nanoparticle platform, which was produced by Ring-Opening Metathesis Polymerization (ROMP), able to release anti-cancer drugs in dispersion, such as histone deacetylase inhibitors, into mesothelioma tumors. The core-shell nanoparticles (NPs) have stealth properties due to their poly(ethylene oxide) shell and can be viewed as universal nano-carriers on which any alkyne-modified anti-cancer molecule can be grafted by click chemistry. A cleavage reaction of the chemical bond between NPs and drugs through the contact of NPs with a medium presenting an acidic pH, which is typically a cancer tumor environment or an acidic intracellular compartment, induces a controlled release of the bioactive molecule in its native form. In our in vivo syngeneic model of mesothelioma, a highly selective accumulation of the particles in the tumor was obtained. The release of the drugs led to an 80% reduction of tumor weight for the best compound without toxicity. Our work demonstrates that the use of theranostic nanovectors leads to an optimized delivery of epigenetic inhibitors in tumors, which improves their anti-tumor properties in vivo.

Recent Progress in Histone Deacetylase Inhibitors as Anticancer Agents

2020 ◽  
Vol 27 (15) ◽  
pp. 2449-2493 ◽  
Author(s):  
Loredana Cappellacci ◽  
Diego R. Perinelli ◽  
Filippo Maggi ◽  
Mario Grifantini ◽  
Riccardo Petrelli
Keyword(s):  
Clinical Trials ◽  
Histone Deacetylase ◽  
Anticancer Agents ◽  
Histone Deacetylase Inhibitors ◽  
Cyclic Peptide ◽  
Hdac Inhibitors ◽  
Cancer Therapeutics ◽  
Rational Drug Design ◽  
Modeling Tools ◽  
Anti Cancer

Histone Deacetylase (HDAC) inhibitors are a relatively new class of anti-cancer agents that play important roles in epigenetic or non-epigenetic regulation, inducing death, apoptosis, and cell cycle arrest in cancer cells. Recently, their use has been clinically validated in cancer patients resulting in the approval by the FDA of four HDAC inhibitors, vorinostat, romidepsin, belinostat and panobinostat, used for the treatment of cutaneous/peripheral T-cell lymphoma and multiple myeloma. Many more HDAC inhibitors are at different stages of clinical development for the treatment of hematological malignancies as well as solid tumors. Also, clinical trials of several HDAC inhibitors for use as anti-cancer drugs (alone or in combination with other anti-cancer therapeutics) are ongoing. In the intensifying efforts to discover new, hopefully, more therapeutically efficacious HDAC inhibitors, molecular modelingbased rational drug design has played an important role. In this review, we summarize four major structural classes of HDAC inhibitors (hydroxamic acid derivatives, aminobenzamide, cyclic peptide and short-chain fatty acids) that are in clinical trials and different computer modeling tools available for their structural modifications as a guide to discover additional HDAC inhibitors with greater therapeutic utility.

Histone Deacetylase Inhibitors and Papillary Thyroid Cancer

2020 ◽  
Vol 26 ◽  
Author(s):  
Eleftherios Spartalis ◽  
Konstantinos Kotrotsios ◽  
Dimosthenis Chrysikos ◽  
Michael Spartalis ◽  
Stavroula A. Paschou ◽  
...  
Keyword(s):  
Thyroid Cancer ◽  
Histone Deacetylase ◽  
Papillary Thyroid Cancer ◽  
Anticancer Agents ◽  
Histone Deacetylase Inhibitors ◽  
Trichostatin A ◽  
Potential Effect ◽  
Papillary Thyroid ◽  
Major Response ◽  
Anti Cancer

Background/Aim: Papillary Thyroid Cancer (PTC) is the most common type of endocrine malignancy. Although PTC has an excellent prognosis, recurrent or metastatic disease could affect patients survival. Recent studies show that Histone Deacetylase Inhibitors (HDACIs) might be promising anticancer agents against PTC. The aim of this review is to evaluate the role of HDACIs as an additional modality in PTC treatment and to depict the latest trends of current research on this field. Materials and Methods: This literature review was performed using the MEDLINE database. The search strategy included terms: “thyroid cancer”, “papillary”, “HDAC”, “histone”, and “deacetylase”. Results: Agents, such as Suberoyl Anilide Hydroxamic Acid, Trichostatin A, Valproic Acid, Sodium butyrate, Panobinostat, Belinostat, Romidepsin, CUDC907 and N-Hydroxy-7-(2-naphthylthio)-Hepanomide have shown promising anti-cancer effects on PTC cell lines but fail to trigger major response in clinical trials. Conclusion: HDACIs have no significant effect as monotherapy against PTC but further research needs to be conducted in order to investigate their potential effect when used as an additional modality.

Recent Progress in the Development of Histone Deacetylase Inhibitors as Anti-Cancer Agents

2013 ◽  
Vol 13 (14) ◽  
pp. 1999-2013 ◽  
Author(s):  
Li Zhang ◽  
Jine Lei ◽  
Yuanyuan Shan ◽  
Hao Yang ◽  
Maxiaowei Song ◽  
...  
Keyword(s):  
Histone Deacetylase ◽  
Recent Progress ◽  
Histone Deacetylase Inhibitors ◽  
Anti Cancer
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