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The apoptotic and genomic studies on A549 cell line induced by silver nitrate
Ayse Kaplan1, Gulsen Akalin Ciftci2, Hatice Mehtap Kutlu1
11 Faculty of Science, Department of Biology, Anadolu University, Eskişehir, Turkey.
Abstract:
Lung cancer is the leading cause of male cancer deaths worldwide. Metal-based anticancer drugs have evolved significantly during the past decades. Recently, silver ions have been investigated for their anticancer effects. We aimed to study the time-course cytotoxic effects of silver nitrate on A549 adenocarcinomic human alveolar basal epithelial cells to provide insights into the molecular-level understanding of growth suppression mechanism involved in apoptosis. The influences of silver nitrate were studied via MTT assay, flow cytometry, immunocytochemical, confocal and transmission electron microscopy, and microarray assays. Silver nitrate showed inhibitory effects against A549 cells in a dose- and time-dependent manner for 24, 48, and 72 h and induced apoptosis. The early and late apoptotic cells and depolarized mitochondrial membrane potential were determined by the half-maximal inhibitory concentration (IC50) value of silver nitrate treated for 72 h. But cysteinyl aspartate proteinase-3 was not activated for 72 h. Furthermore, IC50 value of silver nitrate also induced apoptosis according to immunocytochemical assays for 72 h. The downregulated CCNY, HNRNPL, ASF1B, PIAS4, HNRNPH1, EIF2C2, TAF15, FOXC1, LEP, and PCB2 genes administered with silver nitrate IC50 were identified as apoptosis-leading genes. Silver nitrate may be a suitable therapeutic agent against lung cancer.
Insights
Silver nitrate effectively inhibits lung cancer cell growth and induces apoptosis in a dose- and time-dependent manner. This study identifies key apoptosis-related genes, suggesting silver nitrate
Area of Science:
- Oncology
- Nanomedicine
- Molecular Biology
Background:
- Lung cancer remains a leading cause of cancer mortality globally.
- Metal-based compounds, particularly silver ions, are emerging as potential anticancer agents.
- Understanding the molecular mechanisms of silver-based compounds is crucial for therapeutic development.
Purpose of the Study:
- To investigate the time-course cytotoxic effects of silver nitrate on A549 human lung cancer cells.
- To elucidate the apoptosis-inducing and growth-suppressing mechanisms of silver nitrate at the molecular level.
- To identify potential gene targets involved in silver nitrate-mediated apoptosis.
Main Methods:
- Cytotoxicity was assessed using MTT assays.
- Apoptosis and mitochondrial membrane potential were analyzed via flow cytometry.
- Immunocytochemistry, confocal microscopy, and transmission electron microscopy were employed.
- Gene expression changes were analyzed using microarray assays.
Main Results:
- Silver nitrate demonstrated dose- and time-dependent inhibition of A549 cell proliferation.
- Apoptosis induction and mitochondrial membrane depolarization were observed at the half-maximal inhibitory concentration (IC50) after 72 hours.
- Microarray analysis identified downregulated genes (CCNY, HNRNPL, ASF1B, PIAS4, HNRNPH1, EIF1B, EIF2C2, TAF15, FOXC1, LEP, PCB2) associated with apoptosis.
Conclusions:
- Silver nitrate exhibits significant cytotoxic and apoptosis-inducing effects on A549 lung cancer cells.
- The study provides molecular insights into silver nitrate's anti-cancer activity, highlighting specific gene modulations.
- Silver nitrate shows promise as a potential therapeutic agent for lung cancer treatment.