Cytotoxicity of actinomycetes associated with the ascidian Eudistoma vannamei (Millar, 1977), endemic of northeastern coast of Brazil
Paula C. Jimenez, Elthon G. Ferreira, Luana A. Araújo, Larissa A. Guimarães, Thiciana S. Sousa, Otília Deusdenia L. Pessoa, Tito M. C. Lotufo, Letícia V. Costa-Lotufo
Previous studies demonstrated that the crude extract of the ascidian Eudistoma vannamei, endemic from northeasttern Brazil, strongly hinders growth of tumor cells in vitro by inducing apoptosis due to tryptophan derivatives, which are commonly found in bacteria. This study presents a bioactivity-guided screening among actinomycetes, associated with E. vannamei, aiming at recognizing active principles with biological relevance. Twenty strains of actinomycetes, designated as EVA 0101 through 0120, were isolated from colonies of E. vannamei among which 11 were selected for cytotoxicity evaluation. The extracts from EVA 0102, 0103, 0106, 0109 and 0113 were the most active, and were further studied for IC50 determination and chemical analysis by 1H NMR. IC50 values obtained ranged from 3.62 µg mL-1 (for EVA 0109 in leukemia cells) to 84.65 µg/mL (for EVA 0106 in melanoma cells). All active extracts exhibited the same TLC and spectroscopic profiles, suggesting the presence of quinones and other related secondary metabolites. Furthermore, these strains were identified and compared based on their respective 16S rRNA sequences. The results herein identified the five strains as Micromonospora spp. while phylogenetic analysis suggests that they are possibly two different Micromonospora species producing the cytotoxic compounds.