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Gliclazide may have an antiapoptotic effect related to its antioxidant properties in human normal and cancer cells

Experimental and clinical studies suggest that gliclazide may protect pancreatic β-cells from apoptosis induced by an oxidative stress. However, the precise mechanism(s) of this action are not fully understood and requires further clarification. Therefore, using human normal and cancer cells we exam...

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Autores principales: Sliwinska, Agnieszka, Rogalska, Aneta, Szwed, Marzena, Kasznicki, Jacek, Jozwiak, Zofia, Drzewoski, Jozef
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Springer Netherlands 2011
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3310990/
https://www.ncbi.nlm.nih.gov/pubmed/22183301
http://dx.doi.org/10.1007/s11033-011-1323-z
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author Sliwinska, Agnieszka
Rogalska, Aneta
Szwed, Marzena
Kasznicki, Jacek
Jozwiak, Zofia
Drzewoski, Jozef
author_facet Sliwinska, Agnieszka
Rogalska, Aneta
Szwed, Marzena
Kasznicki, Jacek
Jozwiak, Zofia
Drzewoski, Jozef
author_sort Sliwinska, Agnieszka
collection PubMed
description Experimental and clinical studies suggest that gliclazide may protect pancreatic β-cells from apoptosis induced by an oxidative stress. However, the precise mechanism(s) of this action are not fully understood and requires further clarification. Therefore, using human normal and cancer cells we examined whether the anti-apoptotic effects of this sulfonylurea is due to its free radical scavenger properties. Hydrogen peroxide (H(2)O(2)) as a model trigger of oxidative stress was used to induce cell death. Our experiments were performed on human normal cell line (human umbilical vein endothelial cell line, HUVEC-c) and human cancer cell lines (human mammary gland cell line, Hs578T; human pancreatic duct epithelioid carcinoma cell line, PANC-1). To assess the effect of gliclazide the cells were pre-treated with the drug. The 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide assay was employed to measure the impact of gliclazide on cell viability. Generation of reactive oxygen species, mitochondrial membrane potential (∆Ψ(m)), and intracellular Ca(2+) concentration [Ca(2+)] were monitored. Furthermore, the morphological changes associated with apoptosis were determined using double staining with Hoechst 33258-propidium iodide (PI). Gliclazide protects the tested cells from H(2)O(2)-induced cell death most likely throughout the inhibition of ROS production. Moreover, the drug restored loss of ΔΨ(m) and diminished intracellular [Ca(2+)] evoked by H(2)O(2). Double staining with Hoechst 33258-PI revealed that pre-treatment with gliclazide diminished the number of apoptotic cells. Our findings indicate that gliclazide may protect both normal and cancer human cells against apoptosis induced by H(2)O(2). It appears that the anti-apoptotic effect of the drug is most likely associated with reduction of oxidative stress.
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spelling pubmed-33109902012-03-27 Gliclazide may have an antiapoptotic effect related to its antioxidant properties in human normal and cancer cells Sliwinska, Agnieszka Rogalska, Aneta Szwed, Marzena Kasznicki, Jacek Jozwiak, Zofia Drzewoski, Jozef Mol Biol Rep Article Experimental and clinical studies suggest that gliclazide may protect pancreatic β-cells from apoptosis induced by an oxidative stress. However, the precise mechanism(s) of this action are not fully understood and requires further clarification. Therefore, using human normal and cancer cells we examined whether the anti-apoptotic effects of this sulfonylurea is due to its free radical scavenger properties. Hydrogen peroxide (H(2)O(2)) as a model trigger of oxidative stress was used to induce cell death. Our experiments were performed on human normal cell line (human umbilical vein endothelial cell line, HUVEC-c) and human cancer cell lines (human mammary gland cell line, Hs578T; human pancreatic duct epithelioid carcinoma cell line, PANC-1). To assess the effect of gliclazide the cells were pre-treated with the drug. The 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide assay was employed to measure the impact of gliclazide on cell viability. Generation of reactive oxygen species, mitochondrial membrane potential (∆Ψ(m)), and intracellular Ca(2+) concentration [Ca(2+)] were monitored. Furthermore, the morphological changes associated with apoptosis were determined using double staining with Hoechst 33258-propidium iodide (PI). Gliclazide protects the tested cells from H(2)O(2)-induced cell death most likely throughout the inhibition of ROS production. Moreover, the drug restored loss of ΔΨ(m) and diminished intracellular [Ca(2+)] evoked by H(2)O(2). Double staining with Hoechst 33258-PI revealed that pre-treatment with gliclazide diminished the number of apoptotic cells. Our findings indicate that gliclazide may protect both normal and cancer human cells against apoptosis induced by H(2)O(2). It appears that the anti-apoptotic effect of the drug is most likely associated with reduction of oxidative stress. Springer Netherlands 2011-12-20 2012 /pmc/articles/PMC3310990/ /pubmed/22183301 http://dx.doi.org/10.1007/s11033-011-1323-z Text en © The Author(s) 2011 https://creativecommons.org/licenses/by-nc/4.0/ This article is distributed under the terms of the Creative Commons Attribution Noncommercial License which permits any noncommercial use, distribution, and reproduction in any medium, provided the original author(s) and source are credited.
spellingShingle Article
Sliwinska, Agnieszka
Rogalska, Aneta
Szwed, Marzena
Kasznicki, Jacek
Jozwiak, Zofia
Drzewoski, Jozef
Gliclazide may have an antiapoptotic effect related to its antioxidant properties in human normal and cancer cells
title Gliclazide may have an antiapoptotic effect related to its antioxidant properties in human normal and cancer cells
title_full Gliclazide may have an antiapoptotic effect related to its antioxidant properties in human normal and cancer cells
title_fullStr Gliclazide may have an antiapoptotic effect related to its antioxidant properties in human normal and cancer cells
title_full_unstemmed Gliclazide may have an antiapoptotic effect related to its antioxidant properties in human normal and cancer cells
title_short Gliclazide may have an antiapoptotic effect related to its antioxidant properties in human normal and cancer cells
title_sort gliclazide may have an antiapoptotic effect related to its antioxidant properties in human normal and cancer cells
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3310990/
https://www.ncbi.nlm.nih.gov/pubmed/22183301
http://dx.doi.org/10.1007/s11033-011-1323-z
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