Adamantyl-Substituted Chalcone CA13 Induces Cytoprotective Autophagy and JNK-Dependent Apoptosis in Lung Cancer Cells

Lung cancer remains a leading cause of cancer mortality worldwide, highlighting the need for novel therapeutics. Here, we designed and synthesized a series of adamantyl-substituted chalcones and identified CA13 as a lead compound with potent and selective antiproliferative activity against non-small cell lung cancer (NSCLC) cells. CA13 triggered both apoptosis and autophagy in H292 cells. Western blotting and confocal imaging confirmed the activation of complete autophagic flux, while inhibition of autophagy markedly enhanced CA13-induced apoptosis, suggesting a cytoprotective role of autophagy. Mechanistically, CA13 activated JNK phosphorylation in a dose- and time-dependent manner, and pharmacological blockade of JNK significantly attenuated apoptotic signaling. In vivo, CA13 effectively suppressed H292 xenograft tumor growth without apparent systemic toxicity. Collectively, these results demonstrate that CA13 exerts its antitumor effects through JNK-dependent apoptosis accompanied by cytoprotective autophagy, providing a promising structural framework for the development of chalcone-based anticancer agents targeting programmed cell death pathways.