Exploring the potential of tamoxifen-based copper(ii) 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 of oestrogen receptor alpha (ER alpha). 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(mu-Cl)(L-kappa N-2,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.

Automated summary

This study evaluates the potential of a copper-tamoxifen hybrid complex as a therapeutic candidate for breast cancer. The results show that the complex exhibits remarkable activity against different types of breast cancer cell lines, highlighting its efficacy through diverse mechanisms of action.