Antimicrobial and anticancer activity of Streptomyces ambofaciens (Myt 8) and S. globisporus ONU 1019 (Myt 11) secondary metabolites isolated from the Odesa Bay, the Black Sea: An in vitro study

Abstract

We investigated the antimicrobial and anticancer capacity of secondary metabolites from six strains of marine actinobacteria belonging to the genus Streptomyces. Bacteria strains were isolated from the Black Sea and identified using 16S rRNA gene sequencing. Exometabolites were extracted using ethyl acetate. Antagonistic activity was investigated by agar block-diffusion method against ten strains of indicator microorganisms. The anticancer activities of the extracts were assessed on murine cholangiocarcinoma (CCA) cells while normal mouse fibroblasts CBA-310 served as a control. The extracts were tested as monotherapy or in combination with a standard chemotherapeutic drug for CCA, gemcitabine. Cell proliferation and viability were assessed using crystal violet and cell counting kit-8 assays. The induction of cellular senescence was investigated by senescence-associated β-galactosidase assay. Fluorescence-activated cell sorting analysis was used to determine cellular apoptosis and necroptosis. Liquid chromatography-mass spectrometry (LC-MS/MS) analysis was used to define the main players in the extracts. Streptomyces strains showed antagonistic activity against at least one indicator microorganism. Two extracts, S. ambofaciens (Myt 8) and S. globisporus ONU 1019 (Myt 11), displayed anticancer activity. Extracts Myt 8 and Myt 11 alone or in combination with low doses of gemcitabine inhibited CCA cells in a time and dose-dependent manner and induced early apoptosis and cellular senescence. LC-MS/MS analysis identified daidzein, germicidin, staurosporine alpha-curcumene, and alpha-calacorene - with potential antibacterial and anticancer effects. Streptomyces extracts showed antimicrobial and anticancer properties, potentially reducing chemotherapy doses for CCA. These findings suggest a dual therapeutic role against infections and CCA, warranting further in vivo studies.