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Histone Deacetylases Inhibitor - Valproic Acid Sensitizes Human Melanoma Cells for alkylating agent and PARP inhibitor
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Valproic Acid Sensitizes Human Melanoma Cells for alkylating agent and PARP inhibitor</title> <meta name="description" content="Histone Deacetylases Inhibitor - Valproic Acid Sensitizes Human Melanoma Cells for alkylating agent and PARP inhibitor"> <meta name="keywords" content="melanoma, hdac, parp inhibitor, valproic acid"> <meta name="viewport" content="width=device-width, initial-scale=1, minimum-scale=1, maximum-scale=1, user-scalable=no"> <meta charset="utf-8"> <link href="https://cdn.waset.org/favicon.ico" type="image/x-icon" rel="shortcut icon"> <link href="https://cdn.waset.org/static/plugins/bootstrap-4.2.1/css/bootstrap.min.css" rel="stylesheet"> <link href="https://cdn.waset.org/static/plugins/fontawesome/css/all.min.css" rel="stylesheet"> <link href="https://cdn.waset.org/static/css/site.css?v=150220211555" rel="stylesheet"> </head> <body> <header> <div class="container"> <nav class="navbar navbar-expand-lg navbar-light"> <a class="navbar-brand" href="https://waset.org"> <img src="https://cdn.waset.org/static/images/wasetc.png" alt="Open Science Research Excellence" title="Open Science Research Excellence" /> </a> <button class="d-block d-lg-none navbar-toggler ml-auto" type="button" data-toggle="collapse" data-target="#navbarMenu" aria-controls="navbarMenu" aria-expanded="false" aria-label="Toggle navigation"> <span class="navbar-toggler-icon"></span> </button> <div class="w-100"> <div class="d-none d-lg-flex flex-row-reverse"> <form method="get" action="https://waset.org/search" class="form-inline my-2 my-lg-0"> <input class="form-control mr-sm-2" type="search" placeholder="Search Conferences" value="" name="q" aria-label="Search"> <button class="btn btn-light my-2 my-sm-0" type="submit"><i class="fas fa-search"></i></button> </form> </div> <div class="collapse navbar-collapse mt-1" id="navbarMenu"> <ul class="navbar-nav ml-auto align-items-center" id="mainNavMenu"> <li class="nav-item"> <a class="nav-link" href="https://waset.org/conferences" title="Conferences in 2024/2025/2026">Conferences</a> </li> <li class="nav-item"> <a class="nav-link" href="https://waset.org/disciplines" title="Disciplines">Disciplines</a> </li> <li class="nav-item"> <a class="nav-link" href="https://waset.org/committees" rel="nofollow">Committees</a> </li> <li class="nav-item dropdown"> <a class="nav-link dropdown-toggle" href="#" id="navbarDropdownPublications" role="button" data-toggle="dropdown" aria-haspopup="true" aria-expanded="false"> Publications </a> <div class="dropdown-menu" aria-labelledby="navbarDropdownPublications"> <a class="dropdown-item" href="https://publications.waset.org/abstracts">Abstracts</a> <a class="dropdown-item" href="https://publications.waset.org">Periodicals</a> <a class="dropdown-item" href="https://publications.waset.org/archive">Archive</a> </div> </li> <li class="nav-item"> <a class="nav-link" href="https://waset.org/page/support" title="Support">Support</a> </li> </ul> </div> </div> </nav> </div> </header> <main> <div class="container mt-4"> <div class="row"> <div class="col-md-9 mx-auto"> <form method="get" action="https://publications.waset.org/abstracts/search"> <div id="custom-search-input"> <div class="input-group"> <i class="fas fa-search"></i> <input type="text" class="search-query" name="q" placeholder="Author, Title, Abstract, Keywords" value=""> <input type="submit" class="btn_search" value="Search"> </div> </div> </form> </div> </div> <div class="row mt-3"> <div class="col-sm-3"> <div class="card"> <div class="card-body"><strong>Commenced</strong> in January 2007</div> </div> </div> <div class="col-sm-3"> <div class="card"> <div class="card-body"><strong>Frequency:</strong> Monthly</div> </div> </div> <div class="col-sm-3"> <div class="card"> <div class="card-body"><strong>Edition:</strong> International</div> </div> </div> <div class="col-sm-3"> <div class="card"> <div class="card-body"><strong>Paper Count:</strong> 87408</div> </div> </div> </div> <div class="card publication-listing mt-3 mb-3"> <h5 class="card-header" style="font-size:.9rem">Histone Deacetylases Inhibitor - Valproic Acid Sensitizes Human Melanoma Cells for alkylating agent and PARP inhibitor</h5> <div class="card-body"> <p class="card-text"><strong>Authors:</strong> <a href="https://publications.waset.org/abstracts/search?q=Ma%C5%82gorzata%20Drzewiecka">Małgorzata Drzewiecka</a>, <a href="https://publications.waset.org/abstracts/search?q=Tomasz%20%C5%9Aliwi%C5%84ski"> Tomasz Śliwiński</a>, <a href="https://publications.waset.org/abstracts/search?q=Maciej%20Radek"> Maciej Radek</a> </p> <p class="card-text"><strong>Abstract:</strong></p> The inhibition of histone deacetyles (HDACs) holds promise as a potential anti-cancer therapy because histone and non-histone protein acetylation is frequently disrupted in cancer, leading to cancer initiation and progression. Additionally, histone deacetylase inhibitors (HDACi) such as class I HDAC inhibitor - valproic acid (VPA) have been shown to enhance the effectiveness of DNA-damaging factors, such as cisplatin or radiation. In this study, we found that, using of VPA in combination with talazoparib (BMN-637 – PARP1 inhibitor – PARPi) and/or Dacarabazine (DTIC - alkylating agent) resulted in increased DNA double strand break (DSB) and reduced survival (while not affecting primary melanocytes )and proliferation of melanoma cells. Furthermore, pharmacologic inhibition of class I HDACs sensitizes melanoma cells to apoptosis following exposure to DTIC and BMN-637. In addition, inhibition of HDAC caused sensitization of melanoma cells to dacarbazine and BMN-637 in melanoma xenografts in vivo. At the mRNA and protein level histone deacetylase inhibitor downregulated RAD51 and FANCD2. This study provides that combining HDACi, alkylating agent and PARPi could potentially enhance the treatment of melanoma, which is known for being one of the most aggressive malignant tumors. The findings presented here point to a scenario in which HDAC via enhancing the HR-dependent repair of DSBs created during the processing of DNA lesions, are essential nodes in the resistance of malignant melanoma cells to methylating agent-based therapies. <iframe src="https://publications.waset.org/abstracts/167232.pdf" style="width:100%; height:400px;" frameborder="0"></iframe> <p class="card-text"><strong>Keywords:</strong> <a href="https://publications.waset.org/abstracts/search?q=melanoma" title="melanoma">melanoma</a>, <a href="https://publications.waset.org/abstracts/search?q=hdac" title=" hdac"> hdac</a>, <a href="https://publications.waset.org/abstracts/search?q=parp%20inhibitor" title=" parp inhibitor"> parp inhibitor</a>, <a href="https://publications.waset.org/abstracts/search?q=valproic%20acid" title=" valproic acid"> valproic acid</a> </p> <a href="https://publications.waset.org/abstracts/167232/histone-deacetylases-inhibitor-valproic-acid-sensitizes-human-melanoma-cells-for-alkylating-agent-and-parp-inhibitor" class="btn btn-primary btn-sm">Procedia</a> <a href="https://publications.waset.org/abstracts/167232.pdf" target="_blank" class="btn btn-primary btn-sm">PDF</a> <span class="bg-info text-light px-1 py-1 float-right rounded"> Downloads <span class="badge badge-light">82</span> </span> </div> </div> </div> </main> <footer> <div id="infolinks" class="pt-3 pb-2"> <div class="container"> <div style="background-color:#f5f5f5;" class="p-3"> <div class="row"> <div class="col-md-2"> <ul class="list-unstyled"> About <li><a href="https://waset.org/page/support">About Us</a></li> <li><a href="https://waset.org/page/support#legal-information">Legal</a></li> <li><a target="_blank" rel="nofollow" href="https://publications.waset.org/static/files/WASET-16th-foundational-anniversary.pdf">WASET celebrates its 16th foundational 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