Barman Madhumanti, Kamble Sonam, Roy Sonti, Bhandari Vasundhra, Singothu Siva, Dandasena Debabrata, Suresh Akash, Sharma Paresh
National Institute of Animal Biotechnology (NIAB), Hyderabad, India.
National Institute of Pharmaceutical Education and Research (NIPER), Hyderabad, India.
Front Microbiol. 2021 Nov 18;12:759817. doi: 10.3389/fmicb.2021.759817. eCollection 2021.
The apicomplexan parasite, , is the most prevalent hemoprotozoan in livestock, causing significant economic losses worldwide. It is essential to develop new and improved therapeutics, as current control measures are compromised by the development of resistance against the only available antitheilerial drug, buparvaquone (BPQ). Histone deacetylase inhibitors (HDACi) were shown to treat cancer effectively and revealed antiparasitic activity against apicomplexan parasites such as and . In this study, we investigated the antitheilerial activity of the four anti-cancer HDACi (vorinostat, romidepsin, belinostat, and panobinostat) against the schizont stage of parasites. All four HDACi showed potent activity and increased hyperacetylation of the histone-4 protein. However, based on the low host cell cytotoxicity and IC values, vorinostat (0.103 μM) and belinostat (0.069 μM) were the most effective showing antiparasitic activity. The parasite-specific activities of the HDACi (vorinostat and belinostat) were evaluated by western blotting using parasite-specific antibodies and analysis. Both vorinostat and belinostat reduced the infected cell viability by downregulating anti-apoptotic proteins and mitochondrial dysfunction, leading to caspase-dependent cell apoptosis. The HDACi caused irreversible and antiproliferative effects on the infected cell lines. Our results collectively showed that vorinostat and belinostat could be used as an alternative therapy for treating parasites.
顶复门寄生虫泰勒虫是家畜中最常见的血液原虫，在全球范围内造成重大经济损失。开发新的和改进的治疗方法至关重要，因为目前的控制措施因对唯一可用的抗泰勒虫药物布帕喹（BPQ）产生耐药性而受到影响。组蛋白去乙酰化酶抑制剂（HDACi）已被证明能有效治疗癌症，并显示出对顶复门寄生虫如疟原虫和泰勒虫的抗寄生虫活性。在本研究中，我们研究了四种抗癌HDACi（伏立诺他、罗米地辛、贝利司他和帕比司他）对泰勒虫裂殖体阶段的抗泰勒虫活性。所有四种HDACi均显示出强效活性，并增加了组蛋白-4蛋白的高乙酰化。然而，基于低宿主细胞细胞毒性和IC值，伏立诺他（0.103μM）和贝利司他（0.069μM）是最有效的显示抗寄生虫活性的药物。通过使用寄生虫特异性抗体的蛋白质印迹和分析评估了HDACi（伏立诺他和贝利司他）的寄生虫特异性活性。伏立诺他和贝利司他均通过下调抗凋亡蛋白和线粒体功能障碍降低了感染泰勒虫的细胞活力，导致半胱天冬酶依赖性细胞凋亡。HDACi对感染泰勒虫的细胞系产生不可逆的抗增殖作用。我们的结果共同表明，伏立诺他和贝利司他可作为治疗泰勒虫寄生虫的替代疗法。
需注意，原文中部分寄生虫名称未完整给出，翻译时保留了原文格式。
