Anti-breast cancer effects of a novel derivative of biopigment from Serratia marcescens evoked by mitochondrial pathway-mediated apoptosis

Several secondary metabolites from Serratia marcescens have been reported to show a wide range of cytotoxic and potential antitumor activities. In this study, a novel derivative of bacterial biopigment (Serratin A) was isolated and its structure was characterized using ultraviolet (UV) spectra, infrared (IR) spectra, electronic circular dichroism (ECD) spectra, mass spectrometry (MS) spectra and nuclear magnetic resonance (NMR) spectra. The in vitro assays demonstrated its anticancer activity against the MDA-MB-231, MCF-7, and 4T1 human and mouse breast cancer cell lines. Transcriptomic analyses in MCF-7 cells treated with serratin A (SA) identified specific gene ontology (GO) and kyoto encyclopedia of genes and genomes (KEGG) pathways in differentially expressed genes, particularly the apoptosis pathways enrichment. AnnexinV/propidium iodide staining confirmed apoptosis induction, and the mitochondrial membrane potential (ΔΨm) assay found the ΔΨm value diminished in serratin A-treated cells. Moreover, serratin A treatment increased the pro-apoptotic Bax and Caspase 3/9 while inhibited the anti-apoptotic gene Bcl-2 gene expression in a dose-dependent manner. Finally, serratin A treatment in vivo in MCF-7 tumor-bearing mice showed a dose-dependent tumor growth inhibition accompanied by increased apoptosis. Taken together, we have identified a new compound from Serratia marcescens that exhibits anticancer properties both in vivo and in vitro and has a potential for therapeutic applications in cancer.