2. Academic Validation
  3. Photoaffinity Probe Reveals the Potential Target of Harringtonolide for Cancer Cell Migration Inhibition

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

  • ACS Med Chem Lett. 2022 Feb 2;13(3):449-456. doi: 10.1021/acsmedchemlett.1c00625.
Tian-Yu Zhu 1,  Xiu-Tao Wu 1,  Chen Chen 1,  Xiao-Qin Liu 1,  Li Zhu 1,  Jian-Guang Luo 1,  Ling-Yi Kong 1
Affiliations

Affiliation

  • 1 Jiangsu Key Laboratory of Bioactive Natural Product Research and State Key Laboratory of Natural Medicines, School of Traditional Chinese Pharmacy, China Pharmaceutical University, Nanjing 210009, China.
PMID: 35300090 DOI: 10.1021/acsmedchemlett.1c00625
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.

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