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- Title
HO-3867 Induces ROS-Dependent Stress Response and Apoptotic Cell Death in Leishmania donovani.
- Authors
Das, Amrita; Kamran, Mohd.; Ali, Nahid
- Abstract
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.
- Subjects
LEISHMANIASIS; LEISHMANIA donovani; CELL death; CELL morphology; CELL cycle; LIPOSOMES
- Publication
Frontiers in Cellular & Infection Microbiology, 2021, Vol 11, p1
- ISSN
2235-2988
- Publication type
Article
- DOI
10.3389/fcimb.2021.774899