Luteolin inhibits proliferation of lung cancer A549 cells by increasing ROS production and inhibiting the AKT/mTOR signaling pathway and HO-1 expression.
10.12122/j.issn.1673-4254.2024.12.12
- Author:
Huan LI
1
;
Zixin QIU
1
;
Wenjie XU
1
;
Xue CHEN
1
;
Diandian WEI
1
;
Yun WANG
1
Author Information
1. School of Public Health, Bengbu Medical University, Bengbu 233000, China.
- Publication Type:Journal Article
- Keywords:
AKT/mTOR signaling pathway;
HO-1;
apoptosis;
autophagy;
luteolin;
reactive oxygen species
- MeSH:
Humans;
TOR Serine-Threonine Kinases/metabolism*;
A549 Cells;
Reactive Oxygen Species/metabolism*;
Proto-Oncogene Proteins c-akt/metabolism*;
Cell Proliferation/drug effects*;
Signal Transduction/drug effects*;
Lung Neoplasms/pathology*;
Apoptosis/drug effects*;
Luteolin/pharmacology*;
Autophagy/drug effects*;
Heme Oxygenase-1/metabolism*;
Cell Survival/drug effects*
- From:
Journal of Southern Medical University
2024;44(12):2367-2374
- CountryChina
- Language:Chinese
-
Abstract:
OBJECTIVES:To investigate the mechanism of luteolin for inhibiting proliferation of lung cancer A549 cells.
METHODS:A549 cells treated with different concentrations of luteolin for 48 h were evaluated for changes in cell viability, proliferation, reactive oxygen species (ROS) production and apoptosis using MTT assay, plate cloning assay, EdU staining, DCFH-DA assay and Hoechst33258 staining. The changes in cell autophagy were examined with MDC staining, and the expressions of apoptosis-related proteins (Bax, Bcl-2, and cleaved caspase-9), autophagy-related proteins (LC3B, Beclin 1, and P62), AKT/mTOR pathway proteins, and HO-1 protein were detected using Western blotting.
RESULTS:Treatment with luteolin dose-dependently inhibited the viability and proliferation of A549 cells, increased intracellular ROS levels, up-regulated the expressions of Bax, cleaved caspase-9, and Beclin 1, increased the LC3B-II/LC3B-I ratio, down-regulated the expressions of Bcl-2 and P62, and induced cell apoptosis and autophagy. Luteolin also significantly inhibited the phosphorylation of AKT and mTOR and down-regulated the expression of HO-1 protein in the cells.
CONCLUSIONS:Luteolin induces apoptosis and autophagy to inhibit proliferation of A549 cells by increasing ROS production, inhibiting the AKT/mTOR pathway and down-regulating HO-1 protein expression.