NSAIDs Induce Proline Dehydrogenase/Proline Oxidase-Dependent and Independent Apoptosis in MCF7 Breast Cancer Cells.
COX
NSAIDs
PPAR
apoptosis
breast cancer
mitochondria
oxidative stress
proline dehydrogenase
proline metabolism
proline oxidase
Journal
International journal of molecular sciences
ISSN: 1422-0067
Titre abrégé: Int J Mol Sci
Pays: Switzerland
ID NLM: 101092791
Informations de publication
Date de publication:
30 Mar 2022
30 Mar 2022
Historique:
received:
28
01
2022
revised:
11
03
2022
accepted:
28
03
2022
entrez:
12
4
2022
pubmed:
13
4
2022
medline:
14
4
2022
Statut:
epublish
Résumé
Non-steroidal anti-inflammatory drugs (NSAIDs) are considered in cancer therapy for their inhibitory effect on cyclooxygenase-2 (COX-2), which is overexpressed in most cancers. However, we found that NSAIDs as ligands of peroxisome proliferator-activated receptor-γ (PPARγ)-induced apoptosis independent of the COX-2 inhibition, and the process was mediated through activation of proline dehydrogenase/proline oxidase (PRODH/POX)-dependent generation of reactive oxygen species (ROS). This mitochondrial enzyme converts proline to ∆1-pyrroline-5-carboxylate (P5C) during which ATP or ROS is generated. To confirm the role of PRODH/POX in the mechanism of NSAID-induced apoptosis we obtained an MCF7 CRISPR/Cas9 PRODH/POX knockout breast cancer cell model (MCF7
Identifiants
pubmed: 35409177
pii: ijms23073813
doi: 10.3390/ijms23073813
pmc: PMC8998922
pii:
doi:
Substances chimiques
Anti-Inflammatory Agents, Non-Steroidal
0
Reactive Oxygen Species
0
Proline
9DLQ4CIU6V
Oxidoreductases
EC 1.-
Cyclooxygenase 2
EC 1.14.99.1
Proline Oxidase
EC 1.5.3.-
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : National Science Centre Poland
ID : 2017/27/N/NZ7/02370
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