5-Azacytidine Inhibits the Activation of Senescence Program and Promotes Cytotoxic Autophagy during Trdmt1-Mediated Oxidative Stress Response in Insulinoma β-TC-6 Cells.
5-azacytidine
Trdmt1
autophagy
insulinoma
nitric oxide
oxidative stress
Journal
Cells
ISSN: 2073-4409
Titre abrégé: Cells
Pays: Switzerland
ID NLM: 101600052
Informations de publication
Date de publication:
04 04 2022
04 04 2022
Historique:
received:
27
02
2022
revised:
23
03
2022
accepted:
28
03
2022
entrez:
12
4
2022
pubmed:
13
4
2022
medline:
14
4
2022
Statut:
epublish
Résumé
5-Azacytidine (5-azaC), a methyltransferase inhibitor and anticancer drug, can promote several cellular stress responses such as apoptosis, autophagy, and senescence. The action of 5-azaC is complex and can be modulated by dose, time of treatment, and co-administration with oxidants. Insulinoma is a rare pancreatic neuroendocrine tumor with limited chemotherapeutic options. In the present study, two cellular models of insulinoma were considered, namely NIT-1 and β-TC-6 mouse cells, to evaluate the effects of 5-azaC post-treatment during hydrogen peroxide-induced oxidative stress. 5-azaC attenuated the development of oxidant-induced senescent phenotype in both cell lines. No pro-apoptotic action of 5-azaC was observed in cells treated with the oxidant. On the contrary, 5-azaC stimulated an autophagic response, as demonstrated by the increase in phosphorylated eIF2α and elevated pools of autophagic marker LC3B in oxidant-treated β-TC-6 cells. Notably, autophagy resulted in increased necrotic cell death in β-TC-6 cells with higher levels of nitric oxide compared to less affected NIT-1 cells. In addition, 5-azaC increased levels of RNA methyltransferase Trdmt1, but lowered 5-mC and m
Identifiants
pubmed: 35406777
pii: cells11071213
doi: 10.3390/cells11071213
pmc: PMC8997412
pii:
doi:
Substances chimiques
Antineoplastic Agents
0
Oxidants
0
Methyltransferases
EC 2.1.1.-
Azacitidine
M801H13NRU
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
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