Dihydroartemisinin, a potential PTGS1 inhibitor, potentiated cisplatin-induced cell death in non-small cell lung cancer through activating ROS-mediated multiple signaling pathways.
Neoplasia
; 51: 100991, 2024 05.
Article
in En
| MEDLINE
| ID: mdl-38507887
ABSTRACT
Dihydroartemisinin (DHA) exerts an anti-tumor effect in multiple cancers, however, the molecular mechanism of DHA and whether DHA facilitates the anti-tumor efficacy of cisplatin in non-small cell lung cancer (NSCLC) are unclear. Here, we found that DHA potentiated the anti-tumor effects of cisplatin in NSCLC cells by stimulating reactive oxygen species (ROS)-mediated endoplasmic reticulum (ER) stress, C-Jun-amino-terminal kinase (JNK) and p38 MAPK signaling pathways both in vitro and in vivo. Of note, we demonstrated for the first time that DHA inhibits prostaglandin G/H synthase 1 (PTGS1) expression, resulting in enhanced ROS production. Importantly, silencing PTGS1 sensitized DHA-induced cell death by increasing ROS production and activating ER-stress, JNK and p38 MAPK signaling pathways. In summary, our findings provided new experimental basis and therapeutic prospect for the combined therapy with DHA and cisplatin in some NSCLC patients.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Reactive Oxygen Species
/
Carcinoma, Non-Small-Cell Lung
/
Artemisinins
/
Lung Neoplasms
Limits:
Humans
Language:
En
Journal:
Neoplasia
Journal subject:
NEOPLASIAS
Year:
2024
Document type:
Article
Country of publication:
Estados Unidos