CYTOTOXIC EFFECTS OF SILVER NANOPARTICLES (AgNPs) BIOSYNTHESIZED FROM KLEBSIELLA OXYTOCA DSM29614 AGAINST BREAST CANCER CELLS

Abstract

Klebsiella oxytoca DSM 29614 (KO) is a strain that produces, under anaerobic conditions, bacterial exopolysaccharides (EPSs), made of four rhamnose (Rha), two glucuronic acids (GlcA) and one galactose (Gal) bound by α and β glycosidic bonds1,2, showing metal-binding properties3. In particular, KO in the presence of AgNO3 is able to synthesize silver nanoparticles (AgNPs) incorporated within the EPS (AgNPs-EPS). The AgNPs-EPS, may contain Ag+1 when KO growing in the presence of oxygen and Ag° under anaerobic conditions, giving a different biological activity4. In the present study were evaluated the cytotoxic effects of AgNPs-EPS, produced under aerobic and anaerobic conditions, on breast cancer cell line SK-BR3. Since cancer cells have an altered metabolism in the glycolytic direction (Warburg effect), and utilize glucose as an energy font even in the presence of O2, they are able to sense the presence of the sugar present in the EPS and to pick it with greater efficiency compared to normal cells. Currently, moreover, most of the silver nanoparticles are used as antimicrobial, antifungal, antioxidant and anti-infiammatory agents in biotechnology and bioengineering, in textile engineering and in water treatment, and compared to available cytotoxic chemotherapy, they could afford to developing a biocompatible and cost-effective method of treatment for cancer. The AgNPs-EPS treatments (5 μg/ml) caused a dose dependent behavior resulting in a conspicuous inhibition of cell proliferation rate, dramatic morphological changes with apoptotic features and general proteomic modulation and the most important effects were obtained by treatment with AgNPs-EPS biosynthesised aerobically, which has been demonstrated with voltammetric analysis which issues a greater presence of Ag+1. Proteomic analysis showed modulation of several proteins related to oxidative stress and apoptotic and mitochondrial pathways. Taken together, these results offer new important elements in support of the potential antitumoral activity of AgNPs-EPS.