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 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.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2023 |
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| Erschienen: |
2023 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:75 |
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| Enthalten in: |
Pharmacological reports - 75(2023), 4 vom: 17. Mai, Seite 995-1004 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Miliński, Maciej [VerfasserIn] |
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| Links: |
Volltext [kostenfrei] |
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| Themen: |
Amelanotic melanoma |
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| Anmerkungen: |
© The Author(s) 2023 |
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| doi: |
10.1007/s43440-023-00493-1 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
OLC2144722226 |
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| 245 | 1 | 0 | |a The effect of sulindac on redox homeostasis and apoptosis-related proteins in melanotic and amelanotic cells |
| 264 | 1 | |c 2023 | |
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| 520 | |a 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 | ||
| 650 | 4 | |a Sulindac | |
| 650 | 4 | |a Dacarbazine | |
| 650 | 4 | |a Melanotic melanoma | |
| 650 | 4 | |a Amelanotic melanoma | |
| 650 | 4 | |a Cancer | |
| 650 | 4 | |a p53/Bax/Bcl-2 proteins | |
| 700 | 1 | |a Staś, Monika |0 (orcid)0000-0002-7854-0141 |4 aut | |
| 700 | 1 | |a Rok, Jakub |0 (orcid)0000-0002-8260-4339 |4 aut | |
| 700 | 1 | |a Beberok, Artur |0 (orcid)0000-0003-2247-3004 |4 aut | |
| 700 | 1 | |a Wrześniok, Dorota |0 (orcid)0000-0002-6918-3330 |4 aut | |
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