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Alkaloid derivative ION-31a inhibits breast cancer metastasis and angiogenesis by targeting HSP90α.

Authors :
Ni TW
Duan XC
Wang M
Jia MQ
Chen Y
Yu Y
Qin N
Duan HQ
Source :
Bioorganic chemistry [Bioorg Chem] 2021 Oct; Vol. 115, pp. 105201. Date of Electronic Publication: 2021 Jul 22.
Publication Year :
2021

Abstract

Breast cancer has become the number one killer of women. In our previous study, an active compound, ION-31a, with potential anti-metastasis activity against breast cancer was identified through the synthesis of ionone alkaloid derivatives. In the present study, we aimed to identify the therapeutic target of ION-31a. We used a fluorescence tag labeled probe, molecular docking simulation, and surface plasmon resonance (SPR) analysis to identify the target of ION-31a. The main target of ION-31a was identified as heat shock protein 90 (HSP90). Thus, ION-31a is a novel HSP90 inhibiter that could suppress the metastasis of breast cancer and angiogenesis significantly in vitro and in vivo. ION-31a acts via inhibiting the HSP90/hypoxia inducible factor 1 alpha (HIF-1α)/vascular endothelial growth factor (VEGF)/VEGF receptor 2 (VEGFR2) pathway and downregulating downstream signal pathways, including protein kinase B (AKT)/mammalian target of rapamycin (mTOR), AKT2/protein kinase C epsilon (PKCζ), extracellular regulated kinase 1/2 (ERK1/2), focal adhesion kinase (FAK), and mitogen-activated protein kinase 14 (p38MAPK) pathways. ION-31a affects multiple effectors implicated in tumor metastasis and has the potential to be developed as an anti-metastatic agent to treat patients with breast cancer.<br /> (Copyright © 2021 Elsevier Inc. All rights reserved.)

Details

Language :
English
ISSN :
1090-2120
Volume :
115
Database :
MEDLINE
Journal :
Bioorganic chemistry
Publication Type :
Academic Journal
Accession number :
34329994
Full Text :
https://doi.org/10.1016/j.bioorg.2021.105201