Nimbolide Exhibits Potent Anticancer Activity Through ROS-Mediated ER Stress and DNA Damage in Human Non-small Cell Lung Cancer Cells.
Appl Biochem Biotechnol
; 196(1): 182-202, 2024 Jan.
Article
in En
| MEDLINE
| ID: mdl-37103738
ABSTRACT
The non-small cell lung cancer (NSCLC) accounts for about 85% of all lung cancers. It is usually diagnosed at an advanced stage with poor prognosis. Nimbolide (NB), a terpenoid limonoid isolated from the flowers and leaves of neem tree, possesses anticancer properties in various cancer cell lines. However, the underlying mechanism of its anticancer effect on human NSCLC cells remains unclear. In the present study, we investigated the effect of NB on A549 human NSCLC cells. We found that NB treatment inhibits A549 cells colony formation in a dose-dependent manner. Mechanistically, NB treatment increases cellular reactive oxygen species (ROS) level, leading to endoplasmic reticulum (ER) stress, DNA damage, and eventually induction of apoptosis in NSCLC cells. Furthermore, all these effects of NB were blocked by pretreatment with antioxidant glutathione (GSH), the specific ROS inhibitor. We further knockdown CHOP protein by siRNA markedly reduced NB-induced apoptosis in A549 cells. Taken together, our findings reveal that NB is an inducer of ER stress and ROS; these findings may contribute to increasing the therapeutic efficiency of NSCLC.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Carcinoma, Non-Small-Cell Lung
/
Limonins
/
Lung Neoplasms
Type of study:
Prognostic_studies
Limits:
Humans
Language:
En
Journal:
Appl Biochem Biotechnol
Year:
2024
Type:
Article
Affiliation country:
China