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

© 2023. The Author(s)..

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 H2O2 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 H2O2. 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.

Medienart:

E-Artikel

Erscheinungsjahr:

2023

Erschienen:

2023

Enthalten in:

Zur Gesamtaufnahme - volume:75

Enthalten in:

Pharmacological reports : PR - 75(2023), 4 vom: 17. Aug., Seite 995-1004

Sprache:

Englisch

Beteiligte Personen:

Miliński, Maciej [VerfasserIn]
Staś, Monika [VerfasserIn]
Rok, Jakub [VerfasserIn]
Beberok, Artur [VerfasserIn]
Wrześniok, Dorota [VerfasserIn]

Links:

Volltext

Themen:

184SNS8VUH
Amelanotic melanoma
Antioxidants
Apoptosis Regulatory Proteins
BBX060AN9V
Cancer
Catalase
Dacarbazine
EC 1.11.1.6
EC 1.11.1.9
EC 1.15.1.1
Glutathione Peroxidase
Hydrogen Peroxide
Journal Article
Melanotic melanoma
P53/Bax/Bcl-2 proteins
Sulindac
Superoxide Dismutase

Anmerkungen:

Date Completed 25.09.2023

Date Revised 25.09.2023

published: Print-Electronic

Citation Status MEDLINE

doi:

10.1007/s43440-023-00493-1

funding:

Förderinstitution / Projekttitel:

PPN (Katalog-ID):

NLM356981371