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The effect of sulindac on redox homeostasis and apoptosis-related proteins in melanotic and amelanotic cells

BACKGROUND: Non-steroidal anti-inflammatory drugs have been shown to inhibit the development of induced neoplasms. Our previous research demonstrated that the cytotoxicity of sulindac against melanoma cells is comparable to dacarbazine, the drug used in chemotherapy. The aim of this study was to inv...

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Autores principales: Miliński, Maciej, Staś, Monika, Rok, Jakub, Beberok, Artur, Wrześniok, Dorota
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Springer International Publishing 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10374796/
https://www.ncbi.nlm.nih.gov/pubmed/37195561
http://dx.doi.org/10.1007/s43440-023-00493-1
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author Miliński, Maciej
Staś, Monika
Rok, Jakub
Beberok, Artur
Wrześniok, Dorota
author_facet Miliński, Maciej
Staś, Monika
Rok, Jakub
Beberok, Artur
Wrześniok, Dorota
author_sort Miliński, Maciej
collection PubMed
description BACKGROUND: Non-steroidal anti-inflammatory drugs have been shown to inhibit the development of induced neoplasms. Our previous research demonstrated that the cytotoxicity of sulindac against melanoma cells is comparable to dacarbazine, the drug used in chemotherapy. The aim of this study was to investigate the mechanism of sulindac cytotoxicity on COLO 829 and C32 cell lines. METHODS: The influence of sundilac on the activity of selected enzymes of the antioxidant system (superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx)) and the content of hydrogen peroxide as well as the level of proteins initiating (p53, Bax) and inhibiting (Bcl-2) apoptosis were measured in melanoma cells. RESULTS: In melanotic melanoma cells, sulindac increased the activity of SOD and the content of H(2)O(2) but decreased the activity of CAT and GPx. The level of p53 and Bax proteins rose but the content of Bcl-2 protein was lowered. Similar results were observed for dacarbazine. In amelanotic melanoma cells, sulindac did not cause an increase in the activity of measured enzymes or any significant changes in the level of apoptotic proteins. CONCLUSION: The cytotoxic effect of sulindac in the COLO 829 cell line is connected to disturbed redox homeostasis by changing the activity of SOD, CAT, GPx, and level of H(2)O(2). Sulindac also induces apoptosis by changing the ratio of the pro-apoptotic/anti-apoptotic protein. The presented studies indicate the possibility of developing target therapy against melanotic melanoma using sulindac. GRAPHICAL ABSTRACT: [Image: see text] SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s43440-023-00493-1.
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spelling pubmed-103747962023-07-29 The effect of sulindac on redox homeostasis and apoptosis-related proteins in melanotic and amelanotic cells Miliński, Maciej Staś, Monika Rok, Jakub Beberok, Artur Wrześniok, Dorota Pharmacol Rep Article BACKGROUND: Non-steroidal anti-inflammatory drugs have been shown to inhibit the development of induced neoplasms. Our previous research demonstrated that the cytotoxicity of sulindac against melanoma cells is comparable to dacarbazine, the drug used in chemotherapy. The aim of this study was to investigate the mechanism of sulindac cytotoxicity on COLO 829 and C32 cell lines. METHODS: The influence of sundilac on the activity of selected enzymes of the antioxidant system (superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx)) and the content of hydrogen peroxide as well as the level of proteins initiating (p53, Bax) and inhibiting (Bcl-2) apoptosis were measured in melanoma cells. RESULTS: In melanotic melanoma cells, sulindac increased the activity of SOD and the content of H(2)O(2) but decreased the activity of CAT and GPx. The level of p53 and Bax proteins rose but the content of Bcl-2 protein was lowered. Similar results were observed for dacarbazine. In amelanotic melanoma cells, sulindac did not cause an increase in the activity of measured enzymes or any significant changes in the level of apoptotic proteins. CONCLUSION: The cytotoxic effect of sulindac in the COLO 829 cell line is connected to disturbed redox homeostasis by changing the activity of SOD, CAT, GPx, and level of H(2)O(2). Sulindac also induces apoptosis by changing the ratio of the pro-apoptotic/anti-apoptotic protein. The presented studies indicate the possibility of developing target therapy against melanotic melanoma using sulindac. GRAPHICAL ABSTRACT: [Image: see text] SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s43440-023-00493-1. Springer International Publishing 2023-05-17 2023 /pmc/articles/PMC10374796/ /pubmed/37195561 http://dx.doi.org/10.1007/s43440-023-00493-1 Text en © The Author(s) 2023 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Article
Miliński, Maciej
Staś, Monika
Rok, Jakub
Beberok, Artur
Wrześniok, Dorota
The effect of sulindac on redox homeostasis and apoptosis-related proteins in melanotic and amelanotic cells
title The effect of sulindac on redox homeostasis and apoptosis-related proteins in melanotic and amelanotic cells
title_full The effect of sulindac on redox homeostasis and apoptosis-related proteins in melanotic and amelanotic cells
title_fullStr The effect of sulindac on redox homeostasis and apoptosis-related proteins in melanotic and amelanotic cells
title_full_unstemmed The effect of sulindac on redox homeostasis and apoptosis-related proteins in melanotic and amelanotic cells
title_short The effect of sulindac on redox homeostasis and apoptosis-related proteins in melanotic and amelanotic cells
title_sort effect of sulindac on redox homeostasis and apoptosis-related proteins in melanotic and amelanotic cells
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10374796/
https://www.ncbi.nlm.nih.gov/pubmed/37195561
http://dx.doi.org/10.1007/s43440-023-00493-1
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