2021
DOI: 10.3390/cancers13164217
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Low Doses of Silver Nanoparticles Selectively Induce Lipid Peroxidation and Proteotoxic Stress in Mesenchymal Subtypes of Triple-Negative Breast Cancer

Abstract: Molecular profiling of tumors shows that triple-negative breast cancer (TNBC) can be stratified into mesenchymal (claudin-low breast cancer; CLBC) and epithelial subtypes (basal-like breast cancer; BLBC). Subtypes differ in underlying genetics and in response to therapeutics. Several reports indicate that therapeutic strategies that induce lipid peroxidation or proteotoxicity may be particularly effective for various cancers with a mesenchymal phenotype such as CLBC, for which no specific treatment regimens ex… Show more

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Cited by 11 publications
(18 citation statements)
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“…No increase in absorbance, which could potentially be indicative of increased formazan formation, was observed at any of the AgNP doses tested. In a previous study, using AgNPs identical to those used here, we directly compared the results of the MTT assay with both clonogenic growth and label-free, live cell imaging over time for assessment of the cytotoxicity of AgNPs in a panel of four TNBC and two breast epithelial cell lines [ 54 ]. All three assays were in agreement regarding the relative sensitivity of the cell lines to AgNPs.…”
Section: Discussionmentioning
confidence: 99%
See 1 more Smart Citation
“…No increase in absorbance, which could potentially be indicative of increased formazan formation, was observed at any of the AgNP doses tested. In a previous study, using AgNPs identical to those used here, we directly compared the results of the MTT assay with both clonogenic growth and label-free, live cell imaging over time for assessment of the cytotoxicity of AgNPs in a panel of four TNBC and two breast epithelial cell lines [ 54 ]. All three assays were in agreement regarding the relative sensitivity of the cell lines to AgNPs.…”
Section: Discussionmentioning
confidence: 99%
“…We and others previously showed that AgNPs were highly cytotoxic to multiple TNBC cell lines at doses that were not toxic to non-neoplastic breast cells [ 9 11 , 54 ]. Thus, an extension of our current work on the mechanism of AgNP-induced cell death is the potential to exploit this knowledge for breast cancer therapy.…”
Section: Discussionmentioning
confidence: 99%
“…Silver nanoparticles (AgNPs) are cytotoxic to a variety of cancer cells derived from an assortment of tissues at doses that have a minimal effect on normal cells [ 13 , 14 , 15 , 16 , 17 , 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 36 ]. To the best of the authors’ knowledge, this report is the first use of AgNP as a novel therapy for the treatment of MPNSTs.…”
Section: Discussionmentioning
confidence: 99%
“…AgNPs show a pleiotropic mechanism of action with a variety of cytotoxic effects. Of note, AgNPs are known to induce protein oxidation [ 27 ], DNA damage in the form of double-strand breaks [ 24 , 27 ], misfolded proteins [ 37 ], mitochondrial dysfunction [ 38 ], redox state imbalance [ 24 , 38 ], endoplasmic reticulum stress [ 25 ], and lipid peroxidation [ 36 ]. In general, AgNPs induce catastrophic cell injury in specific subsets of cancer cells, resulting in both apoptotic and necrotic death in breast and lung cancers.…”
Section: Discussionmentioning
confidence: 99%
“…Increased autophagy could be indicative of oxidative damage to proteins and organelles caused by AgNPs, and concerns about AgNP toxicity in general may limit their clinical potential. However, AgNPs have been shown to selectively increase oxidative protein, lipid and DNA damage in some triple-negative breast cancers at doses that do not affect normal breast epithelial cells [ 103 , 104 , 105 , 106 ]. Whether similar selective induction of damage is observed for the treatment of GBM with AgNPs without damaging or radiosensitizing normal brain cells remains to be determined.…”
Section: Metal-based Nanoparticlesmentioning
confidence: 99%