Format

Send to

Choose Destination
Molecules. 2018 Aug 15;23(8). pii: E2046. doi: 10.3390/molecules23082046.

Combination Effect of Silver Nanoparticles and Histone Deacetylases Inhibitor in Human Alveolar Basal Epithelial Cells.

Author information

1
Department of Stem Cell and Regenerative Biotechnology, Konkuk University, Seoul 05029, Korea. gsangiliyandi@yahoo.com.
2
Department of Stem Cell and Regenerative Biotechnology, Konkuk University, Seoul 05029, Korea. pocachippo@gmail.com.
3
Department of Stem Cell and Regenerative Biotechnology, Konkuk University, Seoul 05029, Korea. jhkim541@konkuk.ac.kr.

Abstract

Although many treatment strategies have been reported for lung disease, the mechanism of combination therapy using silver nanoparticles (AgNPs) and histone deacetylases inhibitors (HDACi) remains unclear. Therefore, innovative treatment strategies are essential for addressing the therapeutic challenges of this highly aggressive lung cancer. AgNPs and HDACi seem to be the best candidates for anticancer therapy because of their anti-proliferative effect in a variety of cancer cells. First, we synthesized AgNPs using wogonin as a reducing and stabilizing agent, following which the synthesized AgNPs were characterized by various analytical techniques. The synthesized AgNPs exhibited dose- and size-dependent toxicity towards A549 cells. Interestingly, the combination of AgNPs and MS-275 significantly induces apoptosis, which was accompanied by an increased level of reactive oxygen species (ROS); leakage of lactate dehydrogenase (LDH); secretion of TNFα; dysfunction of mitochondria; accumulation autophagosomes; caspase 9/3 activation; up and down regulation of pro-apoptotic genes and anti-apoptotic genes, respectively; and eventually, induced DNA-fragmentation. Our findings suggest that AgNPs and MS-275 induce cell death in A549 lung cells via the mitochondrial-mediated intrinsic apoptotic pathway. Finally, our data show that the combination of AgNPs and MS-275 is a promising new approach for the treatment of lung cancer and our findings contribute to understanding the potential roles of AgNPs and MS-275 in pulmonary disease. However, further study is warranted to potentiate the use of this combination therapy in cancer therapy trials.

KEYWORDS:

DNA damage; MS-275; apoptosis; autophagosomes; combination therapy; cytotoxicity; oxidative stress; silver nanoparticles

PMID:
30111752
PMCID:
PMC6222610
DOI:
10.3390/molecules23082046
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Multidisciplinary Digital Publishing Institute (MDPI) Icon for PubMed Central
Loading ...
Support Center