Antitheilerial Activity of the Anticancer Histone Deacetylase Inhibitors

The apicomplexan parasite, Theileria annulata, 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 avai...

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Autores principales:	Madhumanti Barman, Sonam Kamble, Sonti Roy, Vasundhra Bhandari, Siva Singothu, Debabrata Dandasena, Akash Suresh, Paresh Sharma
Formato:	article
Lenguaje:	EN
Publicado:	Frontiers Media S.A. 2021
Materias:	drug repurposing HDACi Theileria annulata anticancer molecular docking Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/ab97d99f9e39425c8e22960634766ba1
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spelling	oai:doaj.org-article:ab97d99f9e39425c8e22960634766ba12021-11-19T08:28:47ZAntitheilerial Activity of the Anticancer Histone Deacetylase Inhibitors1664-302X10.3389/fmicb.2021.759817https://doaj.org/article/ab97d99f9e39425c8e22960634766ba12021-11-01T00:00:00Zhttps://www.frontiersin.org/articles/10.3389/fmicb.2021.759817/fullhttps://doaj.org/toc/1664-302XThe apicomplexan parasite, Theileria annulata, 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 in vitro antiparasitic activity against apicomplexan parasites such as Plasmodium and Toxoplasma. In this study, we investigated the antitheilerial activity of the four anti-cancer HDACi (vorinostat, romidepsin, belinostat, and panobinostat) against the schizont stage of T. annulata parasites. All four HDACi showed potent activity and increased hyperacetylation of the histone-4 protein. However, based on the low host cell cytotoxicity and IC50 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 in silico analysis. Both vorinostat and belinostat reduced the Theileria 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 Theileria infected cell lines. Our results collectively showed that vorinostat and belinostat could be used as an alternative therapy for treating Theileria parasites.Madhumanti BarmanSonam KambleSonti RoyVasundhra BhandariSiva SingothuDebabrata DandasenaAkash SureshParesh SharmaFrontiers Media S.A.articledrug repurposingHDACiTheileria annulataanticancermolecular dockingMicrobiologyQR1-502ENFrontiers in Microbiology, Vol 12 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	drug repurposing HDACi Theileria annulata anticancer molecular docking Microbiology QR1-502
spellingShingle	drug repurposing HDACi Theileria annulata anticancer molecular docking Microbiology QR1-502 Madhumanti Barman Sonam Kamble Sonti Roy Vasundhra Bhandari Siva Singothu Debabrata Dandasena Akash Suresh Paresh Sharma Antitheilerial Activity of the Anticancer Histone Deacetylase Inhibitors
description	The apicomplexan parasite, Theileria annulata, 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 in vitro antiparasitic activity against apicomplexan parasites such as Plasmodium and Toxoplasma. In this study, we investigated the antitheilerial activity of the four anti-cancer HDACi (vorinostat, romidepsin, belinostat, and panobinostat) against the schizont stage of T. annulata parasites. All four HDACi showed potent activity and increased hyperacetylation of the histone-4 protein. However, based on the low host cell cytotoxicity and IC50 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 in silico analysis. Both vorinostat and belinostat reduced the Theileria 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 Theileria infected cell lines. Our results collectively showed that vorinostat and belinostat could be used as an alternative therapy for treating Theileria parasites.
format	article
author	Madhumanti Barman Sonam Kamble Sonti Roy Vasundhra Bhandari Siva Singothu Debabrata Dandasena Akash Suresh Paresh Sharma
author_facet	Madhumanti Barman Sonam Kamble Sonti Roy Vasundhra Bhandari Siva Singothu Debabrata Dandasena Akash Suresh Paresh Sharma
author_sort	Madhumanti Barman
title	Antitheilerial Activity of the Anticancer Histone Deacetylase Inhibitors
title_short	Antitheilerial Activity of the Anticancer Histone Deacetylase Inhibitors
title_full	Antitheilerial Activity of the Anticancer Histone Deacetylase Inhibitors
title_fullStr	Antitheilerial Activity of the Anticancer Histone Deacetylase Inhibitors
title_full_unstemmed	Antitheilerial Activity of the Anticancer Histone Deacetylase Inhibitors
title_sort	antitheilerial activity of the anticancer histone deacetylase inhibitors
publisher	Frontiers Media S.A.
publishDate	2021
url	https://doaj.org/article/ab97d99f9e39425c8e22960634766ba1
work_keys_str_mv	AT madhumantibarman antitheilerialactivityoftheanticancerhistonedeacetylaseinhibitors AT sonamkamble antitheilerialactivityoftheanticancerhistonedeacetylaseinhibitors AT sontiroy antitheilerialactivityoftheanticancerhistonedeacetylaseinhibitors AT vasundhrabhandari antitheilerialactivityoftheanticancerhistonedeacetylaseinhibitors AT sivasingothu antitheilerialactivityoftheanticancerhistonedeacetylaseinhibitors AT debabratadandasena antitheilerialactivityoftheanticancerhistonedeacetylaseinhibitors AT akashsuresh antitheilerialactivityoftheanticancerhistonedeacetylaseinhibitors AT pareshsharma antitheilerialactivityoftheanticancerhistonedeacetylaseinhibitors
_version_	1718420278852190208

Antitheilerial Activity of the Anticancer Histone Deacetylase Inhibitors

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