Unknown

Dataset Information

0

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


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.

SUBMITTER: Das A 

PROVIDER: S-EPMC8677699 | biostudies-literature |

REPOSITORIES: biostudies-literature

Similar Datasets

| S-EPMC5427942 | biostudies-literature
| S-EPMC6081962 | biostudies-literature
| S-EPMC7805024 | biostudies-literature
2023-12-31 | GSE217526 | GEO
| S-EPMC7436935 | biostudies-literature
| S-EPMC8370633 | biostudies-literature
| S-EPMC4889150 | biostudies-literature
| S-EPMC5794166 | biostudies-literature
| S-EPMC4726550 | biostudies-literature
| PRJNA210295 | ENA