Histone Deacetylase Inhibitors

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Histone Deacetylase Inhibitors Histone deacetylase (HDAC) inhibitors are a class See the representative list below for a selection of cytostatic agents that inhibit the proliferation of of HDAC inhibitors. tumor cells in various models by inducing cell cycle arrest, differentiation, or apoptosis1. A6132 Apicidin B1746 Belinostat Cells carry out gene expression by controlling the B8275 n-Butyric Acid coiling and uncoiling of DNA around histones. This C2968 Chrysin activity is regulated by histone acetylases, which C8112 CUDC-907 acetylate lysine residues on each histone, loosening E5477 Entinostat chromatin and allowing space for transcription to I7559 Isoliquiritigenin occur. Conversely, HDACs remove acetyl groups L0528 LBH-589 from the lysine residues, forming a more tightly M2409 MGCD-0103 wound, less active chromatin. Inhibiting HDAC P2815 Phenylbutyrate Sodium induces the accumulation of hyperacetylated P2922 Phenylhexyl Isothiocyanate nucleosome core histones in most regions of R5749 Romidepsin chromatin and allows transcription of genes. S1069 Scriptaid HDAC inhibitors can induce p21 gene expression; B8276 Sodium Butyrate p21 is a regulator of tumor suppressor p53 activity. T6933 Trichostatin A HDAC inhibitors can also modulate expression T8000 Tubacin of retinoblastoma, a protein that suppresses cell T8006 Tubastatin A Hydrochloride proliferation. HDAC inhibitor-induced chromatin V0147 Valproic Acid Sodium Salt inactivation and DNA methylation may inhibit V5734 Vorinostat growth and metastasis in centrally-mediated cancers such as glioma2-4. LKT Laboratories carries a variety of HDAC inhibitors that are used in anticancer, antiviral, immunomodulatory, anti-inflammatory, and neuroprotective research applications. References: 1. Dokmanovic M, Clarke C, Marks PA. Mol Cancer Res. 2007 Oct;5(10):981-9. 2. Yin D, Ong JM, Hu J, et al. Clin Cancer Res. 2007 Feb 1;13(3):1045-52. 3. Horing E, Podlech O, Silkenstedt B, et al. Anticancer Res. 2013 Apr;33(4):1351-60. 4. Sharma V, Koul N, Joseph C, et al. J Cell Mol Med. 2010 Inhibition of histone deacetylases induce cell cycle Aug;14(8):2151-61. arrest by interferring with regular DNA coiling Specialty Chemicals for Life Science Research LKT Laboratories, Inc. • lktlabs.com • Phone: 651-644-8424 • Fax: 651-644-8357 .

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Histone Deacetylase Inhibitors: an Attractive Therapeutic Strategy Against Breast Cancer
ANTICANCER RESEARCH 37 : 35-46 (2017) doi:10.21873/anticanres.11286 Review Histone Deacetylase Inhibitors: An Attractive Therapeutic Strategy Against Breast Cancer CHRISTOS DAMASKOS 1,2* , SERENA VALSAMI 3* , MICHAEL KONTOS 4* , ELEFTHERIOS SPARTALIS 2, THEODOROS KALAMPOKAS 5, EMMANOUIL KALAMPOKAS 6, ANTONIOS ATHANASIOU 4, DEMETRIOS MORIS 7, AFRODITE DASKALOPOULOU 2,8 , SPYRIDON DAVAKIS 4, GERASIMOS TSOUROUFLIS 1, KONSTANTINOS KONTZOGLOU 1, DESPINA PERREA 2, NIKOLAOS NIKITEAS 2 and DIMITRIOS DIMITROULIS 1 1Second Department of Propedeutic Surgery, 4First Department of Surgery, Laiko General Hospital, Medical School, National and Kapodistrian University of Athens, Athens, Greece; 2N.S. Christeas Laboratory of Experimental Surgery and Surgical Research, Medical School, National and Kapodistrian University of Athens, Athens, Greece; 3Blood Transfusion Department, Aretaieion Hospital, Medical School, National and Kapodistrian Athens University, Athens, Greece; 5Assisted Conception Unit, Second Department of Obstetrics and Gynecology, Aretaieion Hospital, Medical School, National and Kapodistrian University of Athens, Athens, Greece; 6Gynaecological Oncology Department, University of Aberdeen, Aberdeen, U.K.; 7Lerner Research Institute, Cleveland Clinic, Cleveland, OH, U.S.A; 8School of Biology, National and Kapodistrian University of Athens, Athens, Greece Abstract. With a lifetime risk estimated to be one in eight in anticipate further clinical benefits of this new class of drugs, industrialized countries, breast cancer is the most frequent
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Histone Deacetylase Inhibitory and Cytotoxic Activities of The
Iranian Journal of Basic Medical Sciences ijbms.mums.ac.ir Histone deacetylase inhibitory and cytotoxic activities of the constituents from the roots of three species of Ferula Saba Soltani 1, Gholamreza Amin 1, Mohammad Hossein Salehi-Sourmaghi 1, Mehrdad Iranshahi 2* 1 Department of Pharmacognosy, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran 2 Biotechnology Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Iran A R T I C L E I N F O A B S T R A C T Article type: Objective(s): Histone deacetylase inhibitory and cytotoxic activities of 18 naturally occuring terpenoids Original article (ferutinin, stylosin, tschimgine and guaiol), coumarins (umbelliprenin, farnesiferone B, conferone, Article history: persicasulphides A and C) from the roots of three species of ( and Received: Aug 20, 2018 Ferula Ferula latisecta, Ferula ovina Accepted: Nov 12, 2018 feselol,Ferula flabelliloba ligupersin) wereA, conferdione, evaluated. conferoside) and sulfur-containing derivatives (latisulfies A-E, Materials and Methods: The cytotoxic activity of compounds was evaluated against human cancer cell lines Keywords: (HeLa, HCT116, A2780 and A549) by AlamarBlue® assay using vorinostat as the positive control. On the Apiaceae other hand, we aimed to evaluate their inhibitory activities against pan-HDAC. Ferula latisecta Results: The methanolic extract of the roots of F. flabelliloba was subjected to silica gel column Ferula ovina Ferula flabelliloba Histone deacetylase - isolation of guaiol (1), persicasulphide C (3) and conferoside (10) from the roots of . inhibitors chromatography. Further purification by preparative thin-layer chromatography F.(PTLC) flabelliloba and Cytotoxic activities semipreparative RP-HPLC yielded twelve known compounds (1-12).
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Comparative Effect of Various HDAC-Inhibitors In-Vitro on T- Cell Lymphoma Cell Lines Alone and in Combination with Conventional Anti-Cancer Drugs
Comparative effect of Various HDAC-inhibitors in-vitro on T- Cell Lymphoma cell lines alone and in combination with conventional anti-cancer drugs Arshad H. Banday Mentor:Dr. Francisco Hernandez-Illizaliturri Introduction. T-cell lymphomas are an uncommon and heterogeneous group of non-Hodgkin lymphomas. Historically therapies for these diseases have been borrowed from treatments for other lymphomas. More recently, efforts have be made to identify novel agents for their activity specifically in T-cell lymphomas. A primary example of new agents with specific activity in T-cell lymphomas is the novel class of drug, histone deacetylase inhibitors Vorinostat and romidepsin are currently approved and are in clinical use for the treatment of cutaneous T-cell lymphomas. Intro….. Histones are core structural components of chromatin; DNA is wound around histones, and histones further associate to become and form chromatin. Histone deacetylation inhibitors (HDAC) inhibitors induce accumulation of acetylated histones which leads to relaxation of chromatin structure and promotes access to transcriptional machinery and RNA polymerase HDACi also modify other cancer related proteins. Chromatin Structure Regulates Transcriptional Activity Histone Deacetylase Inhibitors (HDAC Inhibitors) • Cause increased histone acetylation resulting in.. • Uncoiling of chromatin and transcriptional activation of tumor suppressor genes leading to cell cycle arrest and/or apoptosis Currently only Vorinostat is licensed for use in cutaneous T cell lymphoma (CTCL) Genetic
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Epigenetic Reprogramming of Tumor-Associated Fibroblasts in Lung Cancer: Therapeutic Opportunities
cancers Review Epigenetic Reprogramming of Tumor-Associated Fibroblasts in Lung Cancer: Therapeutic Opportunities Jordi Alcaraz 1,2,3,*, Rafael Ikemori 1 , Alejandro Llorente 1 , Natalia Díaz-Valdivia 1 , Noemí Reguart 2,4 and Miguel Vizoso 5,* 1 Unit of Biophysics and Bioengineering, Department of Biomedicine, School of Medicine and Health Sciences, Universitat de Barcelona, 08036 Barcelona, Spain; [email protected] (R.I.); [email protected] (A.L.); [email protected] (N.D.-V.) 2 Thoracic Oncology Unit, Hospital Clinic Barcelona, 08036 Barcelona, Spain; [email protected] 3 Institute for Bioengineering of Catalonia (IBEC), The Barcelona Institute for Science and Technology (BIST), 08028 Barcelona, Spain 4 Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), 08036 Barcelona, Spain 5 Division of Molecular Pathology, Oncode Institute, The Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX Amsterdam, The Netherlands * Correspondence: [email protected] (J.A.); [email protected] (M.V.) Simple Summary: Lung cancer is the leading cause of cancer death among both men and women, partly due to limited therapy responses. New avenues of knowledge are indicating that lung cancer cells do not form a tumor in isolation but rather obtain essential support from their surrounding host tissue rich in altered fibroblasts. Notably, there is growing evidence that tumor progression and even the current limited responses to therapies could be prevented by rescuing the normal behavior of fibroblasts, which are critical housekeepers of normal tissue function. For this purpose, it is key Citation: Alcaraz, J.; Ikemori, R.; to improve our understanding of the molecular mechanisms driving the pathologic alterations of Llorente, A.; Díaz-Valdivia, N.; fibroblasts in cancer.
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Hr23b Expression Is a Potential Predictive Biomarker for HDAC Inhibitor Treatment in Mesenchymal Tumours and Is Associated with Response to Vorinostat
The Journal of Pathology: Clinical Research J Path: Clin Res April 2016; 2: 59–71 Original Article Published online 23 December 2015 in Wiley Online Library (wileyonlinelibrary.com). DOI: 10.1002/cjp2.35 HR23b expression is a potential predictive biomarker for HDAC inhibitor treatment in mesenchymal tumours and is associated with response to vorinostat Michaela Angelika Ihle,1 Sabine Merkelbach-Bruse,1 Wolfgang Hartmann,1,2 Sebastian Bauer,3 Nancy Ratner,4 Hiroshi Sonobe,5 Jun Nishio,6 Olle Larsson,7 Pierre A˚ man,8 Florence Pedeutour,9 Takahiro Taguchi,10 Eva Wardelmann,1,2 Reinhard Buettner1 and Hans-Ulrich Schildhaus1,11* 1 Institute of Pathology, University Hospital Cologne, Cologne, Germany 2 Gerhard Domagk Institute of Pathology, University Hospital M€unster, M€unster, Germany 3 Sarcoma Center, West German Cancer Center, University of Essen, Essen, Germany 4 US Department of Pediatrics, Cincinnati Children’s Hospital Medical Centre, Cincinnati, OH, USA 5 Department of Laboratory Medicine, Chugoku Central Hospital, Fukuyama, Hiroshima, Japan 6 Faculty of Medicine, Department of Orthopaedic Surgery, Fukuoka University, Fukuoka, Japan 7 Department of Oncology and Pathology, The Karolinska Institute, Stockholm, Sweden 8 Sahlgrenska Cancer Centre, University of Gothenburg, Gothenburg, Sweden 9 Faculty of Medicine, Laboratory of Genetics of Solid Tumours, Institute for Research on Cancer and Aging, Nice, France 10 Division of Human Health & Medical Science, Graduate School of Kuroshio Science, Kochi University Nankoku, Kochi, Japan 11 Institute of Pathology, University Hospital G€ottingen, G€ottingen, Germany *Correspondence to: Hans-Ulrich Schildhaus,Institute of Pathology,University Hospital G€ottingen,Robert-Koch-Strasse40,D-37075G€ottingen, Germany.e-mail: [email protected] Abstract Histone deacetylases (HDAC) are key players in epigenetic regulation of gene expression and HDAC inhibitor (HDACi) treatment seems to be a promising anticancer therapy in many human tumours, including soft tissue sar- comas.
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Drug Name Plate Number Well Location % Inhibition, Screen Axitinib 1 1 20 Gefitinib (ZD1839) 1 2 70 Sorafenib Tosylate 1 3 21 Cr
Drug Name Plate Number Well Location % Inhibition, Screen Axitinib 1 1 20 Gefitinib (ZD1839) 1 2 70 Sorafenib Tosylate 1 3 21 Crizotinib (PF-02341066) 1 4 55 Docetaxel 1 5 98 Anastrozole 1 6 25 Cladribine 1 7 23 Methotrexate 1 8 -187 Letrozole 1 9 65 Entecavir Hydrate 1 10 48 Roxadustat (FG-4592) 1 11 19 Imatinib Mesylate (STI571) 1 12 0 Sunitinib Malate 1 13 34 Vismodegib (GDC-0449) 1 14 64 Paclitaxel 1 15 89 Aprepitant 1 16 94 Decitabine 1 17 -79 Bendamustine HCl 1 18 19 Temozolomide 1 19 -111 Nepafenac 1 20 24 Nintedanib (BIBF 1120) 1 21 -43 Lapatinib (GW-572016) Ditosylate 1 22 88 Temsirolimus (CCI-779, NSC 683864) 1 23 96 Belinostat (PXD101) 1 24 46 Capecitabine 1 25 19 Bicalutamide 1 26 83 Dutasteride 1 27 68 Epirubicin HCl 1 28 -59 Tamoxifen 1 29 30 Rufinamide 1 30 96 Afatinib (BIBW2992) 1 31 -54 Lenalidomide (CC-5013) 1 32 19 Vorinostat (SAHA, MK0683) 1 33 38 Rucaparib (AG-014699,PF-01367338) phosphate1 34 14 Lenvatinib (E7080) 1 35 80 Fulvestrant 1 36 76 Melatonin 1 37 15 Etoposide 1 38 -69 Vincristine sulfate 1 39 61 Posaconazole 1 40 97 Bortezomib (PS-341) 1 41 71 Panobinostat (LBH589) 1 42 41 Entinostat (MS-275) 1 43 26 Cabozantinib (XL184, BMS-907351) 1 44 79 Valproic acid sodium salt (Sodium valproate) 1 45 7 Raltitrexed 1 46 39 Bisoprolol fumarate 1 47 -23 Raloxifene HCl 1 48 97 Agomelatine 1 49 35 Prasugrel 1 50 -24 Bosutinib (SKI-606) 1 51 85 Nilotinib (AMN-107) 1 52 99 Enzastaurin (LY317615) 1 53 -12 Everolimus (RAD001) 1 54 94 Regorafenib (BAY 73-4506) 1 55 24 Thalidomide 1 56 40 Tivozanib (AV-951) 1 57 86 Fludarabine
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Entinostat Augments NK Cell Functions Via Epigenetic Upregulation of IFIT1-STING-STAT4 Pathway
www.oncotarget.com Oncotarget, 2020, Vol. 11, (No. 20), pp: 1799-1815 Research Paper Entinostat augments NK cell functions via epigenetic upregulation of IFIT1-STING-STAT4 pathway John M. Idso1, Shunhua Lao1, Nathan J. Schloemer1,2, Jeffrey Knipstein2, Robert Burns3, Monica S. Thakar1,2,* and Subramaniam Malarkannan1,2,4,5,* 1Laboratory of Molecular Immunology and Immunotherapy, Blood Research Institute, Versiti, Milwaukee, WI, USA 2Division of Pediatric Hematology-Oncology-BMT, Department of Pediatrics, Medical College of Wisconsin, Milwaukee, WI, USA 3Bioinformatics Core, Blood Research Institute, Versiti, Milwaukee, WI, USA 4Divson of Hematology-Oncology, Department of Medicine, Medical College of Wisconsin, Milwaukee, WI, USA 5Department of Microbiology and Immunology, Medical College of Wisconsin, Milwaukee, WI, USA *Co-senior authors Correspondence to: Monica S. Thakar, email: [email protected] Subramaniam Malarkannan, email: [email protected] Keywords: NK cells; histone deacetylase inhibitor; Ewing sarcoma; rhabdomyosarcoma; immunotherapy Received: September 10, 2019 Accepted: March 03, 2020 Published: May 19, 2020 Copyright: Idso et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License 3.0 (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. ABSTRACT Histone deacetylase inhibitors (HDACi) are an emerging cancer therapy; however, their effect on natural killer (NK) cell-mediated anti-tumor responses remain unknown. Here, we evaluated the impact of a benzamide HDACi, entinostat, on human primary NK cells as well as tumor cell lines. Entinostat significantly upregulated the expression of NKG2D, an essential NK cell activating receptor. Independently, entinostat augmented the expression of ULBP1, HLA, and MICA/B on both rhabdomyosarcoma and Ewing sarcoma cell lines.
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Drug Screening Approach Combines Epigenetic Sensitization With
Facciotto et al. Clinical Epigenetics (2019) 11:192 https://doi.org/10.1186/s13148-019-0781-3 METHODOLOGY Open Access Drug screening approach combines epigenetic sensitization with immunochemotherapy in cancer Chiara Facciotto1†, Julia Casado1†, Laura Turunen2, Suvi-Katri Leivonen3,4, Manuela Tumiati1, Ville Rantanen1, Liisa Kauppi1, Rainer Lehtonen1, Sirpa Leppä3,4, Krister Wennerberg2 and Sampsa Hautaniemi1* Abstract Background: The epigenome plays a key role in cancer heterogeneity and drug resistance. Hence, a number of epigenetic inhibitors have been developed and tested in cancers. The major focus of most studies so far has been on the cytotoxic effect of these compounds, and only few have investigated the ability to revert the resistant phenotype in cancer cells. Hence, there is a need for a systematic methodology to unravel the mechanisms behind epigenetic sensitization. Results: We have developed a high-throughput protocol to screen non-simultaneous drug combinations, and used it to investigate the reprogramming potential of epigenetic inhibitors. We demonstrated the effectiveness of our protocol by screening 60 epigenetic compounds on diffuse large B-cell lymphoma (DLBCL) cells. We identified several histone deacetylase (HDAC) and histone methyltransferase (HMT) inhibitors that acted synergistically with doxorubicin and rituximab. These two classes of epigenetic inhibitors achieved sensitization by disrupting DNA repair, cell cycle, and apoptotic signaling. The data used to perform these analyses are easily browsable through our Results Explorer. Additionally, we showed that these inhibitors achieve sensitization at lower doses than those required to induce cytotoxicity. Conclusions: Our drug screening approach provides a systematic framework to test non-simultaneous drug combinations. This methodology identified HDAC and HMT inhibitors as successful sensitizing compounds in treatment-resistant DLBCL.
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Histone Deacetylase 3 As a Novel Therapeutic Target in Multiple Myeloma
Leukemia (2014) 28, 680–689 & 2014 Macmillan Publishers Limited All rights reserved 0887-6924/14 www.nature.com/leu ORIGINAL ARTICLE Histone deacetylase 3 as a novel therapeutic target in multiple myeloma J Minami1,4, R Suzuki1,4, R Mazitschek2, G Gorgun1, B Ghosh2,3, D Cirstea1,YHu1, N Mimura1, H Ohguchi1, F Cottini1, J Jakubikova1, NC Munshi1, SJ Haggarty3, PG Richardson1, T Hideshima1 and KC Anderson1 Histone deacetylases (HDACs) represent novel molecular targets for the treatment of various types of cancers, including multiple myeloma (MM). Many HDAC inhibitors have already shown remarkable antitumor activities in the preclinical setting; however, their clinical utility is limited because of unfavorable toxicities associated with their broad range HDAC inhibitory effects. Isoform- selective HDAC inhibition may allow for MM cytotoxicity without attendant side effects. In this study, we demonstrated that HDAC3 knockdown and a small-molecule HDAC3 inhibitor BG45 trigger significant MM cell growth inhibition via apoptosis, evidenced by caspase and poly (ADP-ribose) polymerase cleavage. Importantly, HDAC3 inhibition downregulates phosphorylation (tyrosine 705 and serine 727) of signal transducers and activators of transcription 3 (STAT3). Neither interleukin-6 nor bone marrow stromal cells overcome this inhibitory effect of HDAC3 inhibition on phospho-STAT3 and MM cell growth. Moreover, HDAC3 inhibition also triggers hyperacetylation of STAT3, suggesting crosstalk signaling between phosphorylation and acetylation of STAT3. Importantly, inhibition of HDAC3, but not HDAC1 or 2, significantly enhances bortezomib-induced cytotoxicity. Finally, we confirm that BG45 alone and in combination with bortezomib trigger significant tumor growth inhibition in vivo in a murine xenograft model of human MM.
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Inhibition of Class I Hdacs Abrogates the Dominant Effect of MLL-AF4 by Activation of Wild-Type MLL
OPEN Citation: Oncogenesis (2014) 3, e127; doi:10.1038/oncsis.2014.39 © 2014 Macmillan Publishers Limited All rights reserved 2157-9024/14 www.nature.com/oncsis ORIGINAL ARTICLE Inhibition of class I HDACs abrogates the dominant effect of MLL-AF4 by activation of wild-type MLL K Ahmad1, C Katryniok1, B Scholz2, J Merkens2, D Löscher2, R Marschalek2,3 and D Steinhilber1,3 The ALOX5 gene encodes 5-lipoxygenase (5-LO), a key enzyme of inﬂammatory reactions, which is transcriptionally activated by trichostatin A (TSA). Physiologically, 5-LO expression is induced by calcitriol and/or transforming growth factor-β. Regulation of 5-LO mRNA involves promoter activation and elongation control within the 3′-portion of the ALOX5 gene. Here we focused on the ALOX5 promoter region. Transcriptional initiation was associated with an increase in histone H3 lysine 4 trimethylation in a TSA-inducible manner. Therefore, we investigated the effects of the MLL (mixed lineage leukemia) protein and its derivatives, MLL-AF4 and AF4- MLL, respectively. MLL-AF4 was able to enhance ALOX5 promoter activity by 47-fold, which was further stimulated when either vitamin D receptor and retinoid X receptor or SMAD3/SMAD4 were co-transfected. In addition, we investigated several histone deacetylase inhibitors (HDACi) in combination with gene knockdown experiments (HDAC1-3, MLL). We were able to demonstrate that a combined inhibition of HDAC1-3 induces ALOX5 promoter activity in an MLL-dependent manner. Surprisingly, a constitutive activation of ALOX5 by MLL-AF4 was inhibited by class I HDAC inhibitors, by relieving inhibitory functions deriving from MLL. Conversely, a knockdown of MLL increased the effects mediated by MLL-AF4.
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Valproic Acid and Breast Cancer: State of the Art in 2021
cancers Review Valproic Acid and Breast Cancer: State of the Art in 2021 Anna Wawruszak 1,* , Marta Halasa 1, Estera Okon 1, Wirginia Kukula-Koch 2 and Andrzej Stepulak 1 1 Department of Biochemistry and Molecular Biology, Medical University of Lublin, 20-093 Lublin, Poland; [email protected] (M.H.); [email protected] (E.O.); [email protected] (A.S.) 2 Department of Pharmacognosy, Medical University of Lublin, 20-093 Lublin, Poland; [email protected] * Correspondence: [email protected]; Tel.: +48-81448-6350 Simple Summary: Breast cancer (BC) is the most common cancer diagnosed among women world- wide. Despite numerous studies, the pathogenesis of BC is still poorly understood, and effective therapy of this disease remains a challenge for medicine. This article provides the current state of knowledge of the impact of valproic acid (VPA) on different histological subtypes of BC, used in monotherapy or in combination with other active agents in experimental studies in vitro and in vivo. The comprehensive review highlights the progress that has been made on this topic recently. Abstract: Valproic acid (2-propylpentanoic acid, VPA) is a short-chain fatty acid, a member of the group of histone deacetylase inhibitors (HDIs). VPA has been successfully used in the treatment of epilepsy, bipolar disorders, and schizophrenia for over 50 years. Numerous in vitro and in vivo pre-clinical studies suggest that this well-known anticonvulsant drug signiﬁcantly inhibits cancer cell proliferation by modulating multiple signaling pathways. Breast cancer (BC) is the most common malignancy affecting women worldwide. Despite signiﬁcant progress in the treatment of BC, serious adverse effects, high toxicity to normal cells, and the occurrence of multi-drug resistance (MDR) Citation: Wawruszak, A.; Halasa, M.; still limit the effective therapy of BC patients.
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Histone Deacetylase Inhibitors: a Prospect in Drug Discovery Histon Deasetilaz İnhibitörleri: İlaç Keşfinde Bir Aday
Turk J Pharm Sci 2019;16(1):101-114 DOI: 10.4274/tjps.75047 REVIEW Histone Deacetylase Inhibitors: A Prospect in Drug Discovery Histon Deasetilaz İnhibitörleri: İlaç Keşfinde Bir Aday Rakesh YADAV*, Pooja MISHRA, Divya YADAV Banasthali University, Faculty of Pharmacy, Department of Pharmacy, Banasthali, India ABSTRACT Cancer is a provocative issue across the globe and treatment of uncontrolled cell growth follows a deep investigation in the field of drug discovery. Therefore, there is a crucial requirement for discovering an ingenious medicinally active agent that can amend idle drug targets. Increasing pragmatic evidence implies that histone deacetylases (HDACs) are trapped during cancer progression, which increases deacetylation and triggers changes in malignancy. They provide a ground-breaking scaffold and an attainable key for investigating chemical entity pertinent to HDAC biology as a therapeutic target in the drug discovery context. Due to gene expression, an impending requirement to prudently transfer cytotoxicity to cancerous cells, HDAC inhibitors may be developed as anticancer agents. The present review focuses on the basics of HDAC enzymes, their inhibitors, and therapeutic outcomes. Key words: Histone deacetylase inhibitors, apoptosis, multitherapeutic approach, cancer ÖZ Kanser tedavisi tüm toplum için büyük bir kışkırtıcıdır ve ilaç keşfi alanında bir araştırma hattını izlemektedir. Bu nedenle, işlemeyen ilaç hedeflerini iyileştirme yeterliliğine sahip, tıbbi aktif bir ajan keşfetmek için hayati bir gereklilik vardır. Artan pragmatik kanıtlar, histon deasetilazların (HDAC) kanserin ilerleme aşamasında deasetilasyonu arttırarak ve malignite değişikliklerini tetikleyerek kapana kısıldığını ifade etmektedir. HDAC inhibitörleri, ilaç keşfi bağlamında terapötik bir hedef olarak HDAC biyolojisiyle ilgili kimyasal varlığı araştırmak için, çığır açıcı iskele ve ulaşılabilir bir anahtar sağlarlar.
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