Soluble factors from Aspergillus fumigatus promote NF-κB/AKT/ERK activation and pro-tumor phenotypes in lung cancer cells in vitro.

Role of environmental fungi and Aspergillus fumigatus in respiratory diseases remains evident; however, its contribution to directly influencing lung cancer progression remains obscure. In this study, we investigated the effect of Aspergillus fumigatus extract (AFE) on the development of tumor-promoting characteristics in human lung cancer cell lines. The organism was distinguished based on Lactophenol Cotton Blue staining and further distinguished with protein expression patterns via SDS-PAGE and BCA analysis. A549 and H1299 lung adenocarcinoma human cell lines were challenged with AFE, and various cellular responses were monitored simultaneously for cell viability, proliferative activity, inflammatory gene expression, DNA damage expression, and migratory responses. AFE caused increased cell viability and exhibited cellular characteristics of highly proliferating cells with significant expression of Cyclin D1 and c-MYC. Highly inflammatory gene expression responses and protein expressions of AKT, ERK1/2, and NF-κB signaling pathways were noticed at both the gene and protein expression levels with NF-κB nuclear translocation verified with confocal microscopy studies. DNA damage expression markers like γ-H2AX, p-ATM, and p53 significantly contributed with observable genomic DNA cleavage. Additionally, AFE-exposed cells exhibited faster wound closure and expression of Epithelial-mesenchymal transition-associated factors contributing to cell migration and therapeutic efficacy of this combined approach needs further investigation and development into a targeting therapeutic agent against lung cancer.