Anticancer activity of biogenerated silver nanoparticles: an integrated proteomic investigation

Abstract

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 tested by MTT assay for cytotoxic activity against human breast (SKBR3 and 8701-BC) and colon (HT-29, HCT 116 and Caco-2) cancer cell lines, revealing AgNPs-EPSaer as the most active, in terms of IC50, with a more pronounced efficacy against breast cancer cell lines. Therefore, colony forming capability, morphological changes, generation of reactive oxygen species (ROS), induction of apoptosis and autophagy, inhibition of migratory and invasive capabilities and proteomic changes were investigated using SKBR3 breast cancer cells with the aim to elucidate AgNPs-EPSaer mode of action. In particular, AgNPs-EPSaer induced a significant decrease of cell motility and MMP-2 and MMP-9 activity and a significant increase of ROS generation, which, in turn, supported cell death mainly through autophagy and in a minor extend through apoptosis. Consistently, TEM micrographs and the determination of total silver in subcellular fractions indicated that the Ag+ accumulated preferentially in mitochondria and in smaller concentrations in nucleus, where interact with DNA. Interestingly, these evidences were confirmed by a differential proteomic analysis that highlighted important pathways involved in AgNPs-EPSaer toxicity, including endoplasmic reticulum stress, oxidative stress and mitochondrial impairment triggering cell death trough apoptosis and/or autophagy activation.

Cytotoxic Potential and Molecular Pathway Analysis of Silver Nanoparticles in Human Colon Cancer Cells HCT116

“…We measured MMP in AgNP-treated HCT116 cells using cationic fluorescent dyes [47]. To determine the influence of AgNPs on MMP, HCT116 cells were treated with various concentrations of AgNPs for 24 h, and then, the MMP status was measured.…”

<p>Starch-mediated synthesis of mono- and bimetallic silver/gold nanoparticles as antimicrobial and anticancer agents</p>

“…In recent years, the application of noble metal nanoparticles (NPs), mainly AuNPs and silver NPs (AgNPs), has received considerable attention due to their likely use in diagnostic and therapeutic applications. 13 Although the potent antimicrobial effect and cytotoxicity of AgNPs have been extensively documented, 14,15 AuNPs are considered more biocompatible for a wide range of particle sizes and concentrations. 16 These excellent characteristics add to welltunable plasmonic properties of Au-based nanostructures that have been extensively explored in biomedical applications such as biosensing, X-ray computed tomography contrast and photothermal therapy.…”

Macrophage Metabolomics Reveals Differential Metabolic Responses to Subtoxic Levels of Silver Nanoparticles and Ionic Silver

“…Moreover, the interest in silver nanoparticles beyond their antibacterial action has risen in recent years. This is mainly due to their multiple biological activities, such as the ability to elicit antiviral,, anticancer, and anti‐inflammatory responses , . The interaction of AgNPs with innate immune cells constitutes an important facet of their bioactivity, not only because these cells are key mediators of NP‐induced toxicological outcomes, but also because AgNPs can modulate immune cell functions in the absence of direct cytotoxicity …”