Muhamad, Musthahimah
(2024)
Characterisation Of Biogenic Silver Nanoparticles-garcinia Atroviridis Toxicological Effects In Normal And Cancer Human Lung Cells.
PhD thesis, Universiti Sains Malaysia.
Abstract
Silver nanoparticles (AgNPs) synthesized from plants are increasingly used across various industries, including the pharmaceutical and food sectors. This widespread use has raised concerns about their safety profiles. This study aimed to examine the toxic effects and mechanisms of biogenic silver nanoparticles (AgNPs-GA) synthesized using Garcinia atroviridis leaf extract on human lung cancer cells (A549) and normal lung cells (BEAS-2B) in vitro. Cytotoxicity was evaluated using the MTT assay to determine the IC50 values of AgNPs-GA in both cell types. The IC50 values were applied to treat the respective cells for evaluating reactive oxygen species (ROS) production, apoptosis, DNA damage, silver ion levels, and cellular uptake using CM-H2DCFDA assay, DAPI and AOPI double staining, comet assay, ICP-OES, and TEM, respectively. The mRNA expression and metabolic profiles were further assessed using quantitative real-time PCR and untargeted metabolomics based on ultra-high-performance liquid chromatography-Orbitrap mass spectrometry (UHPLC-Orbitrap-MS), respectively. The results showed that AgNPs-GA inhibited 50% of the growth in A549 and BEAS-2B cells, with IC50 values ranging from 20–28 μg/ml and 12–35 μg/ml, respectively. The selective index (SI) values of AgNPs-GA were below 3, classifying it as a non-selective cytotoxic agent, as it induced general toxicity in both cancerous and non-cancerous cell types. AgNPs-GA were primarily internalized and deposited within lysosomes, nucleus, and mitochondria, leading to an increased release of ionic silver (Ag+) inside both cells.
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