Marine sponge alkaloid aaptamine enhances the anti-bacterial and anti-cancer activity against ESBL producing Gram negative bacteria and HepG 2 human liver carcinoma cells

Abstract

Abstract Marine sponge alkaloid aaptamine is a promising anti-bacterial and anti-cancer drug against ESBL producing Gram negative bacteria and HepG 2 human liver carcinoma cell line. The antibacterial activity of aaptamine against selected ESBL producing Gram negative bacteria was inhibited at the concentration of 55 µg/mL. At the minimum inhibition concentration (MIC) and minimum bactericidal concentration (MBC) of 50 µg/mL, the aaptamine was significantly effective against all the ESBL positive uropathogens. Importantly, the inhibition was much high compared to other marine compounds through intracellular damage and morphological modification by confocal laser scanning electron microscope (CLSM) and scanning electron microscope (SEM). Further, the cytotoxic efficacy of aaptamine against HepG 2 cells was showed at 75 µg/mL very effectively and this concentration was indicated as IC50 dose. The morphological and intracellular nuclear damage of aaptamine treated HepG 2 cell was detected by florescence microscope using acridine orange/ethidium bromide (AO/EB) combination and Hoechst 33342 staining assays. The nuclear fragmentation of aaptamine treated HepG 2 cells were confirmed by expression of Caspase-9, Caspase-8, Caspase-3 cleavage, which provide the suggestion for the induction of intrinsic and extrinsic apoptosis pathways. In addition, the western blot analysis of appatamine treated HepG 2 cells also confirmed that the expression genes were damaged and the aaptamine showed dose and time dependent relationship. Hence, our findings suggest, the marine natural compounds aaptamine might be a potential alternative agents for ESBL producing uropathogens and human liver cancer therapy.