Direct targeting of Capza1 by silibinin

This experiment focused on identifying the direct molecular target of silibinin that mediates F-actin disassembly. The researchers used biochemical approaches to investigate the interaction between silibinin and F-actin regulatory proteins. They discovered that silibinin directly targets Capza1 (capping actin protein of muscle Z-line subunit alpha 1), which is responsible for F-actin disassembly. The study likely employed techniques such as CETSA (cellular thermal shift assay) and DARTS (drug affinity responsive target stability) to demonstrate direct drug-protein interactions. The researchers showed that Capza1-mediated F-actin disassembly is the decisive mechanism for silibinin-induced cell cycle arrest, even when YAP activity is modulated. This experiment revealed a positive feedback loop between YAP and F-actin, where promoting F-actin assembly through si-Capza1 transfection can restore YAP activity.