posted on 2022-02-02, 13:09authored byTian-Yu Zhu, Xiu-Tao Wu, Chen Chen, Xiao-Qin Liu, Li Zhu, Jian-Guang Luo, Ling-Yi Kong
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.