Avermectin induced DNA damage to the apoptosis and autophagy in human lung epithelial A549 cells.

Avermectin (AVM), as a biological insecticide, is widely used in agriculture and forestry production globally. However, inhalation of AVM may pose a risk, and the lung is the direct target, but the cytotoxicity of AVM on human lung cells is still unclear. Here, we attempted to elucidate the cytotoxic effect and molecular mechanism of AVM on human lung A549 cells. The results indicated that AVM inhibits cell proliferation, and enhances programmed cell death (apoptosis and autophagy). In addition, we found the AVM-treated cells showed an obvious drop in mitochondrial membrane potential and LC3-I/II, increased ROS production, DNA double-strand breaks, caspase-3/9 activated, PARP cleaved, cytochrome c and Bax/Bcl-2 content rise. The results showed that AVM induced mitochondria-related apoptosis and autophagy in lung A549 cells. These results indicate that AVM can pose a potential threat to human health by inducing DNA damage and programmed cell death.

Schisandrin B inhibits TGF-ß1-induced epithelial-mesenchymal transition in human A549 cells through epigenetic silencing of ZEB1.

Purpose/Aim: More and more evidences suggest that airway remodeling of fibrotic lung diseases may be associated with epithelial-mesenchymal transition (EMT) of human A549 cells induced by transforming growth factor (TGF)-ß1. Schisandrin B (Sch B) is the highest content of dibenzocyclooctadiene lignans in Schisandra chinensis. In this study, we assessed the inhibitory influences of Sch B on TGF-ß1-stimulated EMT in human A549 cells. Materials and Methods: The influences of Sch B on cell viability, invasion and metastasis in TGF-ß1-induced human A549 cells were detected by MTT, wound healing and transwell invasion assays. The expression levels of α-SMA, E-cadherin, ZEB1 and Twist1 were examined by quantitative reverse transcription polymerase chain reaction (qRT-PCR) and western blot. The enrichment of H3K4me3 and H3K9me3 at the ZEB1 promoter was determined by ChIP analysis. Results: Experimental results showed that Sch B increased the expression of the epithelial phenotype marker E-cadherin and inhibited the expression of the mesenchymal phenotype marker α-SMA during EMT induced by TGF-ß1. The enhancement in invasion and migration of TGF-ß1-induced A549 cells was inhibited by Sch B. Sch B also repressed the expression of ZEB1 transcription factor in EMT, by increasing the enrichment of H3K9me3 at the ZEB1 promoter to repress its transcription while the expression of the Twist1 transcription factor was unaffected. Conclusions: Our data suggest that Sch B can prevent TGF-ß1-stimulated EMT in A549 cells through epigenetic silencing of ZEB1, which may be clinically related to the efficient treatment of EMT-associated fibrotic diseases.

Surface-modified magnetite nanoparticles act as aneugen-like spindle poison.

Iron oxide nanoparticles are one of the most promising types of nanoparticles for biomedical applications, primarily in the context of nanomedicine-based diagnostics and therapy; hence, great attention should be paid to their bio-safety. Here, we investigate the ability of surface-modified magnetite nanoparticles (MNPs) to produce chromosome damage in human alveolar A549 cells. Compared to control cells, all the applied MNPs increased the level of micronuclei moderately but did not cause structural chromosomal aberrations in exposed cells. A rise in endoreplication, polyploid and multinuclear cells along with disruption of tubulin filaments, downregulation of Aurora protein kinases and p53 protein activation indicated the capacity of these MNPs to impair the chromosomal passenger complex and/or centrosome maturation. We suppose that surface-modified MNPs may act as aneugen-like spindle poisons via interference with tubulin polymerization. Further studies on experimental animals revealing mechanisms of therapeutic-aimed MNPs are required to confirm their suitability as potential anti-cancer drugs.