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

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...

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Main Authors: Dominik Żyro, Agnieszka Śliwińska, Izabela Szymczak-Pajor, Małgorzata Stręk, Justyn Ochocki
Format: Article
Language:English
Published: MDPI AG 2020-12-01
Series:Cancers
Subjects:
Online Access:https://www.mdpi.com/2072-6694/12/12/3848
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author Dominik Żyro
Agnieszka Śliwińska
Izabela Szymczak-Pajor
Małgorzata Stręk
Justyn Ochocki
author_facet Dominik Żyro
Agnieszka Śliwińska
Izabela Szymczak-Pajor
Małgorzata Stręk
Justyn Ochocki
author_sort Dominik Żyro
collection DOAJ
description 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<sub>3</sub>, 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.
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spelling doaj.art-6656a11dba1444fa8c9272a23dd090752023-11-21T01:45:20ZengMDPI AGCancers2072-66942020-12-011212384810.3390/cancers12123848Light Stability, Pro-Apoptotic and Genotoxic Properties of Silver (I) Complexes of Metronidazole and 4-Hydroxymethylpyridine against Pancreatic Cancer Cells In VitroDominik Żyro0Agnieszka Śliwińska1Izabela Szymczak-Pajor2Małgorzata Stręk3Justyn Ochocki4Departament of Bioinorganic Chemistry, Chair of Medicinal Chemistry, Medical University of Łódź, Muszyńskiego 1, 90-151 Łódź, PolandDepartment of Nucleic Acids Biochemistry, Medical University of Łódź, Pomorska 251, 92-213 Łódź, PolandDepartment of Nucleic Acids Biochemistry, Medical University of Łódź, Pomorska 251, 92-213 Łódź, PolandDepartment of Nucleic Acids Biochemistry, Medical University of Łódź, Pomorska 251, 92-213 Łódź, PolandDepartament of Bioinorganic Chemistry, Chair of Medicinal Chemistry, Medical University of Łódź, Muszyńskiego 1, 90-151 Łódź, PolandAntimicrobial 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<sub>3</sub>, 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.https://www.mdpi.com/2072-6694/12/12/3848cytotoxicityapoptosisgenotoxicitymedicinal chemistrysilver (I)complex
spellingShingle Dominik Żyro
Agnieszka Śliwińska
Izabela Szymczak-Pajor
Małgorzata Stręk
Justyn Ochocki
Light Stability, Pro-Apoptotic and Genotoxic Properties of Silver (I) Complexes of Metronidazole and 4-Hydroxymethylpyridine against Pancreatic Cancer Cells In Vitro
Cancers
cytotoxicity
apoptosis
genotoxicity
medicinal chemistry
silver (I)
complex
title Light Stability, Pro-Apoptotic and Genotoxic Properties of Silver (I) Complexes of Metronidazole and 4-Hydroxymethylpyridine against Pancreatic Cancer Cells In Vitro
title_full Light Stability, Pro-Apoptotic and Genotoxic Properties of Silver (I) Complexes of Metronidazole and 4-Hydroxymethylpyridine against Pancreatic Cancer Cells In Vitro
title_fullStr Light Stability, Pro-Apoptotic and Genotoxic Properties of Silver (I) Complexes of Metronidazole and 4-Hydroxymethylpyridine against Pancreatic Cancer Cells In Vitro
title_full_unstemmed Light Stability, Pro-Apoptotic and Genotoxic Properties of Silver (I) Complexes of Metronidazole and 4-Hydroxymethylpyridine against Pancreatic Cancer Cells In Vitro
title_short Light Stability, Pro-Apoptotic and Genotoxic Properties of Silver (I) Complexes of Metronidazole and 4-Hydroxymethylpyridine against Pancreatic Cancer Cells In Vitro
title_sort light stability pro apoptotic and genotoxic properties of silver i complexes of metronidazole and 4 hydroxymethylpyridine against pancreatic cancer cells in vitro
topic cytotoxicity
apoptosis
genotoxicity
medicinal chemistry
silver (I)
complex
url https://www.mdpi.com/2072-6694/12/12/3848
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