Calyxin Y induces hydrogen peroxide-dependent autophagy and apoptosis via JNK activation in human non-small cell lung cancer NCI-H460 cells

Calyxin Y has been recently isolated from Alpinia katsumadai which has a folk use as an anti-tumor medicine. Calyxin Y induced caspase-dependent cell death in NCI-H460 cells, and concomitantly, provoked cytoprotective autophagy with the upregulation of critical Atg proteins. The cleavage of Atg proteins by caspases acted as a switch between autophagy and apoptosis induced by calyxin Y. Intracellular hydrogen peroxide (H₂O₂) production was triggered upon exposure to calyxin Y via the induction of autophagy and apoptosis. We provided evidence that activated JNK was upstream effectors controlling both autophagy and apoptosis in response to elevated H₂O₂. Therefore, our findings demonstrate that calyxin Y serves multiple roles as a promising chemotherapeutic agent that induces H₂O₂-dependent autophagy and apoptosis via JNK activation.