Exploring the potential of tamoxifen-based copper() dichloride in breast cancer therapy

For decades, tamoxifen-based hormone therapy has effectively addressed oestrogen receptor positive (ER+) luminal A breast cancer. Nonetheless, the emergence of tamoxifen resistance required innovative approaches, leading to hybrid metallodrugs with several therapeutic effects besides the inhibition...

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Bibliographic Details
Published in:MedChemComm 2023-12, Vol.14 (12), p.2574-2582
Main Authors: Kazimir, Aleksandr, Schwarze, Benedikt, Lönnecke, Peter, Jela a, Sanja, Mijatovi, Sanja, Maksimovi -Ivani, Danijela, Hey-Hawkins, Evamarie
Format: Article
Language:English
Subjects:
Apoptosis
Breast cancer
Breast carcinoma
Cancer therapies
Chemistry
Copper
Copper chloride
Dichlorides
Effectiveness
Estrogen receptors
Glioblastoma
Metabolites
Metal compounds
Palladium
Receptors
Tamoxifen
Transition metal compounds
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Summary:For decades, tamoxifen-based hormone therapy has effectively addressed oestrogen receptor positive (ER+) luminal A breast cancer. Nonetheless, the emergence of tamoxifen resistance required innovative approaches, leading to hybrid metallodrugs with several therapeutic effects besides the inhibition of oestrogen receptor α (ERα). Drawing inspiration from tamoxifen metabolite structures (4-hydroxytamoxifen and 4,4′-dihyroxytamoxifen), a phenyl ring was replaced by a bidentate 2,2′-bipyridine donor moiety to give 4-[1,1-bis(4-methoxyphenyl)but-1-en-2-yl]-2,2′-bipyridine ( L ), enabling coordination of bioactive transition metal compounds such as copper( ii ) dichloride, yielding [CuCl(μ-Cl)( L -κ 2 N , N ′)] 2 ( 1 ). Notably, copper( ii ) complex 1 exhibited remarkable activity within the low micromolar concentration range against ER+ human glioblastoma U251, as well as breast carcinomas MDA-MB-361 and MCF-7, surpassing the efficacy of previously reported palladium( ii ) and platinum( ii ) dichloride analogs against these cell lines. The pronounced efficacy of complex 1 against triple-negative MDA-MB-231 cells highlights its potential multitherapeutic approach, evident through induction of apoptosis and antioxidant activity. This study evaluates the potential of copper-tamoxifen hybrid complex 1 as a potent therapeutic candidate, highlighting its diverse mechanism of action against challenging breast cancer subtypes. This study explores a copper-tamoxifen hybrid drug as a promising alternative to platinum complexes in breast cancer therapy, offering a new mechanism of action.
ISSN:2632-8682
2040-2503
2632-8682
2040-2511
DOI:10.1039/d3md00344b