Light Stability, Pro-Apoptotic and Genotoxic Properties of Silver (I) Complexes of Metronidazole and 4-Hydroxymethylpyridine against Pancreatic Cancer Cells In Vitro

SIMPLE SUMMARY: Antimicrobial 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. ABSTRACT: 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 AgNO(3), 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.