Staurosporine from Streptomyces sanyensis activates Programmed Cell Death in Acanthamoeba via the mitochondrial pathway and presents low in vitro cytotoxicity levels in a macrophage cell line

• Published in: Scientific reports Vol. 9; no. 1; pp. 11651 - 12
• Main Authors: Cartuche, Luis, Sifaoui, Ines, Cruz, Darío, Reyes-Batlle, María, López-Arencibia, Atteneri, Javier Fernández, José, Díaz-Marrero, Ana R., Piñero, José E., Lorenzo-Morales, Jacob
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 12.08.2019; Nature Publishing Group
• Subjects: 13/2; 14; 14/19; 14/63; 631/154/309; 631/326/417; Acanthamoeba; Acanthamoeba castellanii - cytology; Acanthamoeba castellanii - drug effects; Actinomycetes; Amebiasis - drug therapy; Amebiasis - parasitology; Amebicides - isolation & purification; Amebicides - pharmacology; Amebicides - therapeutic use; Animals; Apoptosis; Apoptosis - drug effects; Aquatic Organisms - chemistry; Bioactive compounds; Cell activation; Cell death; Cell Line; Cell lines; Cytotoxicity; Humanities and Social Sciences; Humans; Indolocarbazoles; Life cycles; Macrophages; Macrophages - drug effects; Marine microorganisms; Membrane Potential, Mitochondrial - drug effects; Mice; Microorganisms; Mitochondria; Mitochondria - drug effects; multidisciplinary; Natural resources; Parasites; Phenols; Protozoa; Science; Science (multidisciplinary); Staurosporine; Staurosporine - isolation & purification; Staurosporine - pharmacology; Staurosporine - therapeutic use; Streptomyces; Streptomyces - chemistry; Toxicity Tests, Acute; Trophozoites - cytology; Trophozoites - drug effects
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-019-48261-7

Recently, the search for novel therapeutic agents against Acanthamoeba species has been focused on the evaluation of natural resources. Among them, marine microorganisms have risen as a source of bioactive compounds with the advantage of the ability to obtain unlimited and constant amounts of the compounds in contrast to other natural sources such as plants. Furthermore, marine actinomycetes have recently been reported as highly rich in bioactive agents including salinosporamides, xiamycines, indolocarbazoles, naphtyridines, phenols, dilactones such as antimycines and macrolides among others. In this study, staurosporine (STS) was isolated from a strain of Streptomyces sanyensis and tested against Acanthamoeba to characterize the therapeutic potential of STS against this protozoan parasite. We have established that STS is active against both stages of the Acanthamoeba life cycle, by the activation of Programmed Cell Death via the mitochondrial pathway of the trophozoite. We have also established that STS has relatively low toxicity towards a macrophage cell line. However, previous studies have highlighted higher toxicity levels induced on other vertebrate cell lines and future research to lower these toxicity issues should be developed.