HO-3867 Induces ROS-Dependent Stress Response and Apoptotic Cell Death in Leishmania donovani

Lack of vaccine and increasing chemotherapeutic toxicities currently necessitate the development of effective and safe drugs against various forms of leishmaniases. We characterized the cellular stress induced by a novel curcumin analogue, HO-3867, encapsulated within the phosphatidylcholine-stearyl...

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Autores principales:	Amrita Das, Mohd. Kamran, Nahid Ali
Formato:	article
Lenguaje:	EN
Publicado:	Frontiers Media S.A. 2021
Materias:	liposome stress Leishmania donovani HO-3867 apoptosis Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/279f164ac0604ddf9dd64127ce206766
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spelling	oai:doaj.org-article:279f164ac0604ddf9dd64127ce2067662021-12-03T04:53:36ZHO-3867 Induces ROS-Dependent Stress Response and Apoptotic Cell Death in Leishmania donovani2235-298810.3389/fcimb.2021.774899https://doaj.org/article/279f164ac0604ddf9dd64127ce2067662021-12-01T00:00:00Zhttps://www.frontiersin.org/articles/10.3389/fcimb.2021.774899/fullhttps://doaj.org/toc/2235-2988Lack of vaccine and increasing chemotherapeutic toxicities currently necessitate the development of effective and safe drugs against various forms of leishmaniases. We characterized the cellular stress induced by a novel curcumin analogue, HO-3867, encapsulated within the phosphatidylcholine-stearylamine (PC-SA) liposome for the first time against Leishmania. The liposomal formulation of HO-3867 (i.e., PC-SA/HO-3867) initiated oxidative stress-induced apoptosis in L. donovani, revealed by altered cell morphology, phosphatidylserine externalization, mitochondrial depolarization, intracellular lipid accumulation, and cell cycle arrest in promastigotes. Liposomal HO-3867 was observed to be a strong apoptosis inducer in L. donovani and L. major in a dose-dependent manner, yet completely safe for normal murine macrophages. Moreover, PC-SA/HO-3867 treatment induced L. donovani metacaspase and PARP1 activation along with downregulation of the Sir2 gene. PC-SA/HO-3867 arrested intracellular L. donovani amastigote burden in vitro, with reactive oxygen species (ROS) and nitric oxide (NO)-mediated parasite killing. These data suggest that liposomal HO-3867 represents a highly promising and non-toxic nanoparticle-based therapeutic platform against leishmaniasis inspiring further preclinical developments.Amrita DasMohd. KamranNahid AliFrontiers Media S.A.articleliposomestressLeishmania donovaniHO-3867apoptosisMicrobiologyQR1-502ENFrontiers in Cellular and Infection Microbiology, Vol 11 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	liposome stress Leishmania donovani HO-3867 apoptosis Microbiology QR1-502
spellingShingle	liposome stress Leishmania donovani HO-3867 apoptosis Microbiology QR1-502 Amrita Das Mohd. Kamran Nahid Ali HO-3867 Induces ROS-Dependent Stress Response and Apoptotic Cell Death in Leishmania donovani
description	Lack of vaccine and increasing chemotherapeutic toxicities currently necessitate the development of effective and safe drugs against various forms of leishmaniases. We characterized the cellular stress induced by a novel curcumin analogue, HO-3867, encapsulated within the phosphatidylcholine-stearylamine (PC-SA) liposome for the first time against Leishmania. The liposomal formulation of HO-3867 (i.e., PC-SA/HO-3867) initiated oxidative stress-induced apoptosis in L. donovani, revealed by altered cell morphology, phosphatidylserine externalization, mitochondrial depolarization, intracellular lipid accumulation, and cell cycle arrest in promastigotes. Liposomal HO-3867 was observed to be a strong apoptosis inducer in L. donovani and L. major in a dose-dependent manner, yet completely safe for normal murine macrophages. Moreover, PC-SA/HO-3867 treatment induced L. donovani metacaspase and PARP1 activation along with downregulation of the Sir2 gene. PC-SA/HO-3867 arrested intracellular L. donovani amastigote burden in vitro, with reactive oxygen species (ROS) and nitric oxide (NO)-mediated parasite killing. These data suggest that liposomal HO-3867 represents a highly promising and non-toxic nanoparticle-based therapeutic platform against leishmaniasis inspiring further preclinical developments.
format	article
author	Amrita Das Mohd. Kamran Nahid Ali
author_facet	Amrita Das Mohd. Kamran Nahid Ali
author_sort	Amrita Das
title	HO-3867 Induces ROS-Dependent Stress Response and Apoptotic Cell Death in Leishmania donovani
title_short	HO-3867 Induces ROS-Dependent Stress Response and Apoptotic Cell Death in Leishmania donovani
title_full	HO-3867 Induces ROS-Dependent Stress Response and Apoptotic Cell Death in Leishmania donovani
title_fullStr	HO-3867 Induces ROS-Dependent Stress Response and Apoptotic Cell Death in Leishmania donovani
title_full_unstemmed	HO-3867 Induces ROS-Dependent Stress Response and Apoptotic Cell Death in Leishmania donovani
title_sort	ho-3867 induces ros-dependent stress response and apoptotic cell death in leishmania donovani
publisher	Frontiers Media S.A.
publishDate	2021
url	https://doaj.org/article/279f164ac0604ddf9dd64127ce206766
work_keys_str_mv	AT amritadas ho3867inducesrosdependentstressresponseandapoptoticcelldeathinleishmaniadonovani AT mohdkamran ho3867inducesrosdependentstressresponseandapoptoticcelldeathinleishmaniadonovani AT nahidali ho3867inducesrosdependentstressresponseandapoptoticcelldeathinleishmaniadonovani
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HO-3867 Induces ROS-Dependent Stress Response and Apoptotic Cell Death in Leishmania donovani

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