You‐Cheng HseuYu‐Chi HuangVaradharajan ThiyagarajanDony Chacko MathewKai‐Yuan LinSsu‐Ching ChenJer‐Yuh LiuLi‐Sung HsuMei‐Ling LiHsin‐Ling Yang2026-01-292026-01-292019-03-0710.1002/jcp.28375https://scholars.csmu.edu.tw/handle/123456789/3847<jats:title>Abstract</jats:title><jats:p>Chalcones found in fruits and vegetables have promising cancer chemopreventive properties. This study attempts to identify the anticancer efficacies of chalcone flavokawain B (FKB) in the rhizomes of <jats:italic>Alpinia pricei</jats:italic> Hayata by examining key molecular events in non‐small‐cell lung cancer (A549) cells. Our results indicated that in human A549 cells, FKB (0–15 μg/ml) decreases cell viability and colony formation, dysregulates the Bax:B‐cell lymphoma 2 ratio and increases apoptotic DNA fragmentation. Mitochondrial (caspase‐9/‐3 and poly ADP ribose polymerase [PARP]) signaling was found to be involved in FKB‐induced apoptosis. In addition, FKB‐induced reactive oxygen species (ROS) generation, and <jats:italic>N</jats:italic>‐acetylcysteine attenuated FKB‐induced apoptotic cell death. Moreover, FKB triggered autophagy, as evidenced by the improved acidic vesicular organelle formation, lipidated light chain 3 (microtubule‐related light chain 3) accumulation, and ATG7 expression and the decreased mammalian target of rapamycin phosphorylation. Furthermore, FKB suppressed ROS‐mediated ATG4B expression. Inhibiting autophagy using 3‐methyladenine/chloroquine diminished FKB‐induced cell death, indicating that autophagy is triggered as a death mechanism by FKB. In summary, FKB has a crucial role in the execution and propagation of ROS‐mediated apoptotic and autophagic cell death of lung adenocarcinoma cells.</jats:p>[SDGs]SDG3journal-article