Atractylodin induces apoptosis and autophagy of lung cancer cells via ROS/Nrf2/HO-1 signaling pathway
10.3969/j.issn.1000-4718.2024.11.008
- VernacularTitle:苍术素通过ROS/Nrf2/HO-1信号通路诱导肺癌细胞凋亡和自噬
- Author:
Zhenhui WU
1
;
Hongmiao WANG
;
Jingyi LI
;
Meigui YOU
;
Yaping XU
Author Information
1. 福建医科大学公共卫生学院,福建 福州 350122
- Keywords:
atractylodin;
lung cancer;
apoptosis;
autophagy;
ROS/Nrf2/HO-1 signaling pathway
- From:
Chinese Journal of Pathophysiology
2024;40(11):2050-2058
- CountryChina
- Language:Chinese
-
Abstract:
AIM:This study investigates the apoptotic and autophagic effects of atractylodin on lung cancer cells,elucidating the underlying molecular mechanisms.METHODS:Non-small cell lung cancer(NSCLC)A549 and H460 cells,in addition to non-cancerous HBE cells,were cultured in vitro.The effects of atractylodin at various concen-trations on cell viability were assessed using CCK-8 assay.Apoptotic effects were evaluated through Hoechst staining and flow cytometry,while Western blot analysis was performed to detect changes in protein expressions associated with apopto-sis and autophagy,including P62,beclin-1,microtubule-associated protein 1 light chain 3(LC3),Kelch-like epichloro-hydrin(ECH)-associated protein-1(Keap-1),nuclear factor E2-related factor 2(Nrf2),heme oxygenase-1(HO-1),and NAD(P)H:quinone oxidoreductase 1(NQO1).Autophagic flux was further analyzed using acridine orange(AO)stain-ing,and immunofluorescence for LC3 and Nrf2.Additionally,autophagy inhibition experiments were conducted using chloroquine(CQ),followed by analyses of autophagy and apoptosis.Reactive oxygen species(ROS)levels were quanti-fied using DCFH-DA.RESULTS:Treatment with atractylodin significantly reduced the viability of A549 and H460 lung cancer cells,promoting apoptosis and inducing autophagy.This was evidenced by an increase in acidic autophagic vesi-cles,upregulation of LC3 and beclin-1,and downregulation of P62.Inhibition of autophagy by chloroquine reversed atrac-tylodin-induced apoptosis.Moreover,atractylodin heightened ROS production,inhibited Keap-1,and stimulated the ex-pression of Nrf2,HO-1 and NQO1.CONCLUSION:Atractylodin effectively inhibits the proliferation of lung cancer cells by inducing apoptosis and autophagy.These effects are mediated through the modulation of the ROS/Nrf2/HO-1 sig-naling pathway,underscoring its potential as a therapeutic agent in lung cancer treatment.
