Apoptotic Induction in Human Cancer Cell Lines by Antimicrobial Compounds from Antarctic Streptomyces fildesensis (INACH3013)

Abstract

The Antarctic Streptomyces fildesensis has been recognized for its production of antimicrobial compounds with interesting biological activities against foodborne bacteria and multi-resistant strains, but not for its potential antiproliferative activity and mechanisms involved. Two bioactive ethyl acetate extract (EAE) fractions were purified via thin-layer chromatography and High-Performance Liquid Chromatography (HPLC), showing that orange-colored compounds displayed antimicrobial activity against pathogenic bacteria even after shock thermal treatment. The UV–VIS features of the active compounds, the TLC assay with actinomycin-D pure standard, Fourier transform infrared (FTIR) spectra and the ANTISMASH analysis support the presence of actinomycin-like compounds. We demonstrated that S. fildesensis displays antiproliferative activity against human tumor cell lines, including human breast cancer (MCF-7), prostate cancer (PC-3), colon cancer (HT-29) and non-tumoral colon epithelial cells (CoN). The half-maximal effective concentrations (EC50) ranged from 3.98 µg/mL to 0.1 µg/mL. Our results reveal that actinomycin-like compounds of S. fildesensis induced apoptosis mediated by caspase activation, decreasing the mitochondrial membrane potential and altering the cell morphology in all tumoral and non-tumoral cell lines analyzed. These findings confirm the potential of the psychrotolerant Antarctic S. fildesensis species as a promising source for obtaining potential novel anticancer compounds.