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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

Year: 2025

Type: article

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. Antimicrobial and anticancer activity of Streptomyces strains S. ambofaciens (Myt 8) and S. globisporus ONU 1019 (Myt 11). Strains were collected in the Odesa Bay of the Black Sea (the collection site: Odesa, Ukraine, 46°27′01′′N 30°46′14′′E, shown on the map). (A) Strain S. ambofaciens (Myt 8) demonstrated activity against nosocomial pathogens such as S. aureus ATCC 25923 and C. albicans ATCC 18804 on Gauze 1 and Oat agar media. In the extract form, Myt 8 demonstrated a significant anticancer activity in CVSA and CCK-8 tests, induced early apoptosis and cellular senescence in CCA cells. Several natural compounds such as daidzein, staurosporine, alpha-curcumene, and alpha-calacorene were detected in the extract of Myt 8. (B) Strain S. globisporus ONU 1019 (Myt 11) demonstrated activity аgainst a wide range of pathogens, including bacteria that cause biliary infections/inflammation and ACC. In the extract form, Myt 11 exhibited a high cytotoxic and antiproliferative capacity in CCA, which was detected using CVSA and CCK-8 tests, respectively; induced early apoptosis and cellular senescence in CCA cells. Several natural compounds such as daidzein, germicidin, and alpha-curcumene were found in the Myt 11 extract. CVSA - crystal violet staining assay; CCK-8 - cell counting kit – 8; GEM - Gemcitabine; G1 - Gauze 1; G2 - Gauze 2; O/a - oat agar; conc. – concentration. • Marine Streptomyces strains were collected from the Odesa Bay in the Black Sea. • S. ambofaciens (Myt 8) demonstrated activity against nosocomial pathogens. • S. globisporus ONU 1019 (Myt 11) inhibited several biliary tracts´ pathogens. • Extracts Myt 8 and Myt 11 inhibited the growth of cholangiocarcinoma (CCA) cells. • Key compounds: daidzein, germicidin, staurosporine, alpha-curcumene and -calacorene.

Source: Biomedicine & Pharmacotherapy

DOI: 10.1016/j.biopha.2025.117981