Photoaffinity Probe Reveals the Potential Target of Harringtonolide for Cancer Cell Migration Inhibition.

Harringtonolide ( HO , 1 ) is a bioactive diterpenoid tropone isolated from Cephalotaxus harringtonia with antiproliferation activity. Until now there have been no reports to elucidate its anticancer mechanism. Herein we report the synthesis of HO -derived probes ( 10 , 11 , and 12 ) to identify the possible target of HO . As a result, the application of a novel photoaffinity alkyne-tagged probe from HO (compound 12 ) showed direct engagement between HO and receptor for activated C kinase 1 (RACK1). Furthermore, HO could suppress the epithelial-mesenchymal transition (EMT) process and inhibit activation of the FAK/Src/STAT3 signaling pathway in A375 cells. This study provides a groundwork for HO as an effective antitumor agent that targets RACK1 to suppress cancer cell migration.