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 possibl...

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Published in:ACS medicinal chemistry letters 2022-03, Vol.13 (3), p.449-456
Main Authors: Zhu, Tian-Yu, Wu, Xiu-Tao, Chen, Chen, Liu, Xiao-Qin, Zhu, Li, Luo, Jian-Guang, Kong, Ling-Yi
Format: Article
Language:English
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Letter
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Summary: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.
ISSN:1948-5875
1948-5875
DOI:10.1021/acsmedchemlett.1c00625