Abstract
Simple SummaryAntimicrobial properties of silver (I) ion and its complexes with metronidazole and 4-hydroxymethylpyridine are well recognized. However, little is known about its anticancer activity toward human pancreatic cancer cells. Our in vitro study revealed that silver (I) ion and its complexes with metronidazole and 4-hydroxymethylpyridine induced pancreatic cancer cells death associated with genotoxic and proapoptotic properties. In turn, the stability of active substances is of crucial importance because it determines the efficacy and applicability in clinical use. Therefore, we also evaluated photostability of silver (I) nitrate and its complexes with metronidazole and 4- hydroxymethylpyridine. Our results showed that studied complexes are more photochemically stable than silver salts, which makes them better candidates for clinical therapy.Antimicrobial properties of silver (I) ion and its complexes are well recognized. However, recent studies suggest that both silver (I) ion and its complexes possess anticancer activity associated with oxidative stress-induced apoptosis of various cancer cells. In this study, we aimed to investigate whether silver nitrate and its complexes with metronidazole and 4-hydroxymethylpyridine exert anticancer action against human pancreatic cancer cell lines (PANC-1 and 1.2B4). In the study, we compared decomposition speed for silver complexes under the influence of daylight and UV-A (ultraviolet-A) rays. We employed the MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazonium bromide) assay to evaluate the cytotoxicity and the alkaline comet assay to determine genotoxicity of silver nitrate and its complexes. Flow cytometry and the Annexin V-FITC/PI apoptosis detection kit were used to detect the apoptosis of human pancreatic cancer cells. We found a dose dependent decrease of both pancreatic cancer cell line viability after exposure to silver nitrate and its complexes. The flow cytometry analysis confirmed that cell death occurred mainly via apoptosis. We also documented that the studied compounds induced DNA damage. Metronidazole and 4-hydroxymethylpyridine alone did not significantly affect viability and level of DNA damage of pancreatic cancer cell lines. Complex compounds showed better stability than AgNO3, which decomposed slower than when exposed to light. UV-A significantly influences the speed of silver salt decomposition reaction. To conclude, obtained data demonstrated that silver nitrate and its complexes exerted anticancer action against human pancreatic cancer cells.
Highlights
Numerous studies have revealed that metal ions and their complexes have cytotoxic and genotoxic activity
We aimed to evaluate whether cytotoxicity of silver nitrate and its complexes may be a result of apoptosis
The synthesis of the complex of the silver ion with metronidazole in the form of a nitrate salt presented in our earlier papers [9,17]
Summary
Numerous studies have revealed that metal ions and their complexes have cytotoxic and genotoxic activity. These properties, especially of complex compounds with well know ligands, are still under extensive investigation as effective drugs for treating various disease, including cancers and those evoked by microorganisms. The pharmacological properties of silver preparations are determined by the specific biological activity of Ag(I) ions, which arise as a result of the dissociation of its compounds. One of the main pharmacological properties of the preparations is their antimicrobial activity. It was demonstrated that silver ions (silver nitrate) exerted cytotoxic and genotoxic properties against different human cells via oxidative stress production [8,9]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
