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Anticancer activity of biogenerated silver nanoparticles: an integrated proteomic investigation
Silver nanoparticles (AgNPs), embedded into a specific polysaccharide (EPS), were biogenerated by DSM 29614 under aerobic (AgNPs-EPS ) and anaerobic conditions (AgNPs-EPS ). Both AgNPs-EPS matrices were tested by MTT assay for cytotoxic activity against human breast (SKBR3 and 8701-BC) and colon (HT...
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Published in: | Oncotarget 2018-02, Vol.9 (11), p.9685-9705 |
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Main Authors: | , , , , , , , , , , |
Format: | Article |
Language: | English |
Subjects: | |
Citations: | Items that this one cites Items that cite this one |
Online Access: | Get full text |
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Summary: | Silver nanoparticles (AgNPs), embedded into a specific polysaccharide (EPS), were biogenerated by
DSM 29614 under aerobic (AgNPs-EPS
) and anaerobic conditions (AgNPs-EPS
). 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-EPS
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-EPS
mode of action. In particular, AgNPs-EPS
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-EPS
toxicity, including endoplasmic reticulum stress, oxidative stress and mitochondrial impairment triggering cell death trough apoptosis and/or autophagy activation. |
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ISSN: | 1949-2553 1949-2553 |
DOI: | 10.18632/oncotarget.23859 |