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.
Highlights
Cancer is still a prevalent disease, and lung cancer is one of the most fatal chronic diseases
The rate of synthesis and color formation was higher at 60 ◦ C compared with that at 40 ◦ C, which is due to the increased temperature allowing particle growth at a higher rate; it is favorable for the synthesis of smaller-sized particles [26]
The results from our study indicate that AgNPs or MS-275 or a combination of AgNPs and MS-275 induces cytotoxicity on human lung cancer cells, we could not distinguish between necrosis and apoptosis
Summary
Cancer is still a prevalent disease, and lung cancer is one of the most fatal chronic diseases. It has been the second most common cause of cancer-related death in both men and women worldwide, for several decades. Lung cancer is mainly found in elderly people aged 65 or older worldwide. According to a report in 2012, 1,800,000 new lung cancer cases were estimated and diagnosed worldwide and as a result of lung cancer, approximately 1,590,000 people were killed [1,2]. Lung disease is associated with deregulated apoptosis. According to 2012 data, lung cancer killed 24%
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