Apoptotic-like activity of staurosporine in axenic cultures of Trypanosoma evansi

Abstract

SUMMARYTrypanosoma evansi is a blood protozoan parasite of the genus Trypanosoma which is responsible for surra (Trypanosomosis) in domestic and wild animals. This study addressed apoptotic-like features in Trypanosoma evansi in vitro. The mechanism of parasite death was investigated using staurosporine as an inducing agent. We evaluated its effects through several cytoplasmic features of apoptosis, including cell shrinkage, phosphatidylserine exposure, maintenance of plasma membrane integrity, and mitochondrial trans-membrane potential. For access to these features we have used the flow cytometry and fluorescence microscopy with cultures in the stationary phase and adjusted to a density of 10 6 cells/mL. The apoptotic effect of staurosporine in T. evansi was evaluated at 20 nM final concentration. There was an increase of phosphatidylserine exposure, whereas mitochondrial potential was decreased. Moreover, no evidence of cell permeability increasing with staurosporine was observed in this study, suggesting the absence of a necrotic process. Additional studies are needed to elucidate the possible pathways associated with this form of cell death in this hemoparasite.

Antiamoebic Activities of Indolocarbazole Metabolites Isolated from Streptomyces sanyensis Cultures

“…STS has exhibited promising inhibitory activity against parasites [10,11,12]; since protein kinases (PKs) play critical roles in the growth and mechanism of infection of some parasites such as Trypanosoma and Leishmania spp., and parasitic PKs differ from their mammal counterparts, these antibiotics result attractive for the development of specific inhibitors [13]. Additionally, it has been demonstrated that STS induced cell death in blood forms of Trypanosoma brucei in a dose-dependent manner, stimulating the activation of apoptosis by releasing EndoG from mitochondrial disruption under ROS production [14]; however, to the best of our knowledge there is no information about the antiparasitic effect of streptocarbazole B, 4′-demethylamino-4′-oxostaurosporine, and 7-oxostaurosporine which are the focus of this research.…”

Evaluation of Indolocarbazoles from Streptomyces sanyensis as a Novel Source of Therapeutic Agents against the Brain-Eating Amoeba Naegleria fowleri

“…In this study, we aimed to evaluate the potential activity of four natural ICZs (1-4) previously isolated from the culture of the S. sanyensis PBLC04 strain which was collected from a mangrove in Ecuador [22][23][24]. All the mentioned compounds are reported PK inhibitors and have shown activity against other parasitic protozoa such as various species of Leishmania, Trypanosoma cruzi, and the Acanthamoeba genus [22,23,27,32]. Furthermore, activity assays revealed that STS (1) and 7OSTS (2) were the most active molecules, presenting IC 50 values ranging from 0.08 ± 0.02 to 1.28 ± 0.35 µM, against both strains of N. fowleri, and lower levels of cytotoxicity than miltefosine after performance of toxicity assays (Table 1).…”

“…Indolocarbazoles including STS have been previously reported to present protein kinase (PK) and/or DNA topoisomerase I inhibition properties [22,[25][26][27][28][29][30]. Furthermore, focusing on PK inhibitors with STS the most studied one, these enzymes are key ones in pathways of infection and survival of parasitic protozoa [31][32][33]. Moreover, STS treatment has been related to the induction of programmed cell death (PCD) or apoptotic-like processes via the interaction with PK and/or mitochondrial disruption mechanisms [22,24,34].…”