Afzelin induces immunogenic cell death against lung cancer by targeting NQO2

BACKGROUND: Lung cancer is one of the most common malignant cancers worldwide. Previous studies have shown that Afzelin, a flavonoid, possesses anticancer activity. The aim of this study was to explore Afzelin’s effect on lung cancer cells and delineate potential anti-cancer mechanism. METHODS: The effect of Afzelin on cell viability, proliferation, and apoptosis of lung cancer cells i.e., A549 and H1299 cells, was studied. The targets for Afzelin in lung cancer were predicted using SwissTargetPrediction, Next, the GO analysis and pathway enrichment were analyzed using String. For in vitro studies, the overexpression plasmid of NQO2, the identified target of Afzelin, was transfected into Afzelin-treated cells to verify the regulatory role of Afzelin on its target and signaling pathway. RESULTS: In in vitro studies, Afzelin markedly inhibited cell viability, proliferation, and raised apoptotic rate of A549 and H1299 cells. In addition, Afzelin activated endoplasmic reticulum (ER) stress and increased ATP, HMGB1, and CRT levels in lung cancer cells, indicating that Afzelin induced immunogenic cell death (ICD). SwissTargetPrediction identified NQO2 as a target of Afzelin. Further, Afzelin markedly inhibited NQO2 protein expression and in turn, overexpression of NQO2 attenuated the effect of Afzelin on A549 and H1299 cells. CONCLUSION: Afzelin inhibits lung cancer progression by targeting NQO2, in turn, activating ER stress and inducing ICD. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12906-023-04221-3.