Imperial College London
Alternate

Dr Ernesto Yagüe

Faculty of Medicine, Department of Surgery & Cancer

Non-Clinical Lecturer in Cancer Cell Biology
 
 
 
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Contact

 

+44 (0)20 7594 2802ernesto.yague Website

 
 
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Location

 

Cancer Research Centre, room 135ICTEM buildingHammersmith Campus

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Summary

 

Publications

Citation

BibTex format

@article{Li:2019:10.1021/acsmedchemlett.9b00284,
author = {Li, D-D and Yagüe, E and Wang, L-Y and Dai, L-L and Yang, Z-B and Zhi, S and Zhang, N and Zhao, X-M and Hu, Y-H},
doi = {10.1021/acsmedchemlett.9b00284},
journal = {ACS Medicinal Chemistry Letters},
pages = {1328--1335},
title = {Novel copper complexes that inhibit the proteasome and trigger apoptosis in triple-negative breast cancer cells},
url = {http://dx.doi.org/10.1021/acsmedchemlett.9b00284},
volume = {10},
year = {2019}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - Five innovative ternary copper(II) complexes [Cu(OH-PIP)(Phe)Cl](1), [Cu(OH-PIP)(Gly)(H2O)]NO3·2H2O (2), [Cu(OH-PIP)(Ala)(Cl)]·H2O (3), [Cu(OH-PIP)(Met)]PF6·2H2O (4), and [Cu(OH-PIP)(Gln)(H2O)](Cl)·3H2O (5) have been synthesized and characterized by infrared spectroscopy, elemental analysis, and single crystal X-ray diffraction analysis. X-ray crystallography indicates that all Cu atoms are five-coordinated in a square-pyramidal configuration. The complexes have been screened for cytotoxicity against human breast cancer cell lines MCF-7, MDA-MB-231, and CAL-51. The best anticancer activity is obtained with triple-negative breast cancer CAL-51 and MDA-MB-231 cell lines, with IC50 values in the range of 0.082-0.69 μM. Importantly, the copper compounds were more effective than carboplatin at triggering cell death. Mechanistically, the complexes inhibit proteasomal chymotrypsin-like activity, and docking studies reveal their 20S proteasome binding sites. As a consequence, they cause the accumulation of ubiquitinated proteins, inhibit cell proliferation, and induce apoptosis. In addition, these copper complexes decrease the stemness of triple-negative breast cancer cells and have synergistic effects with CBP on TNBC cells, indicating their great potential as a novel therapy for triple-negative breast cancer.
AU  - Li,D-D
AU  - Yagüe,E
AU  - Wang,L-Y
AU  - Dai,L-L
AU  - Yang,Z-B
AU  - Zhi,S
AU  - Zhang,N
AU  - Zhao,X-M
AU  - Hu,Y-H
DO  - 10.1021/acsmedchemlett.9b00284
EP  - 1335
PY  - 2019///
SN  - 1948-5875
SP  - 1328
TI  - Novel copper complexes that inhibit the proteasome and trigger apoptosis in triple-negative breast cancer cells
T2  - ACS Medicinal Chemistry Letters
UR  - http://dx.doi.org/10.1021/acsmedchemlett.9b00284
UR  - https://www.ncbi.nlm.nih.gov/pubmed/31531205
UR  - http://hdl.handle.net/10044/1/73583
VL  - 10
ER  -
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