Silver nanoparticles (AgNPs), embedded into a specific polysaccharide (EPS),were biogenerated by Klebsiella oxytoca DSM 29614 under aerobic (AgNPs-EPSaer)and anaerobic conditions (AgNPs-EPSanaer). Both AgNPs-EPS matrices were testedby MTT assay for cytotoxic activity against human breast (SKBR3 and 8701-BC) andcolon (HT-29, HCT 116 and Caco-2) cancer cell lines, revealing AgNPs-EPSaer as themost active, in terms of IC50, with a more pronounced efficacy against breast cancercell lines. Therefore, colony forming capability, morphological changes, generationof reactive oxygen species (ROS), induction of apoptosis and autophagy, inhibitionof migratory and invasive capabilities and proteomic changes were investigatedusing SKBR3 breast cancer cells with the aim to elucidate AgNPs-EPSaer mode ofaction. In particular, AgNPs-EPSaer induced a significant decrease of cell motility andMMP-2 and MMP-9 activity and a significant increase of ROS generation, which, inturn, supported cell death mainly through autophagy and in a minor extend throughapoptosis. Consistently, TEM micrographs and the determination of total silver insubcellular fractions indicated that the Ag+ accumulated preferentially in mitochondriaand in smaller concentrations in nucleus, where interact with DNA. Interestingly,these evidences were confirmed by a differential proteomic analysis that highlightedimportant pathways involved in AgNPs-EPSaer toxicity, including endoplasmic reticulumstress, oxidative stress and mitochondrial impairment triggering cell death troughapoptosis and/or autophagy activation.
|Numero di pagine||21|
|Stato di pubblicazione||Published - 2018|
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