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

ABSTRACT: 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.

SUBMITTER: Zhu TY

PROVIDER: S-EPMC8919390 | biostudies-literature | 2022 Mar

REPOSITORIES: biostudies-literature

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

Zhu Tian-Yu TY Wu Xiu-Tao XT Chen Chen C Liu Xiao-Qin XQ Zhu Li L Luo Jian-Guang JG Kong Ling-Yi LY

ACS medicinal chemistry letters 20220202 3

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 enga ...[more]

PMID: 35300090

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