Application of Aescin-Loaded Chitosan Nanoparticles for Enhancement of DNA Damage and Associated cGAS Pathway in A549 Lung Cancer Cells.

Abstract

The cGAS-STING pathway plays a central role in detecting cytosolic DNA in addition to initiating immune responses against tumor cells. The present study investigates the efficacy of Aescin-loaded chitosan nanoparticles (AESC-CSNPs) in enhancing DNA damage and associated cGAS pathway in A549 lung cancer cells. AESC-CSNPs were synthesized using the ionic gelation method, and characterization was performed to analyze the particle size, surface charge, and encapsulation efficiency. A549 lung cancer cells treated with AESC-CSNPs displayed augmented levels of DNA damage indications, such as γ-H2AX, signifying more DNA double-strand breaks. Western blotting showed higher levels of cGAS, STING, and phosphorylated TBK1, specifying the initiation of the cGAS-STING cascade. Furthermore, the increase of mainstream cytokines, such as IFN-β and IL-6, was confirmed by qRT-PCR, indicating a pro-inflammatory response by the immune system. Annexin V/PI discoloration and flow cytometry further displayed that AESC-CSNPs induced apoptosis in association with DNA damage. These results suggested that AESC-CSNPs could induce damage in the DNA of A549 lung cancer cells, contributing to an initiation of cGAS, with its associated anti-tumor response. Thus, this study identifies AESC-CSNPs as a promising strategy to affect the A549 cells to immune shadowing and apoptosis by the associated cGAS-STING pathway.

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