AI Summary
Tamoxifen-based hormone therapy has been effective in treating ER+ luminal A breast cancer, but the development of tamoxifen resistance has led to the creation of hybrid metallodrugs. One of these drugs, copper(II) complex 1, has shown promising results against ER+ breast cancer and glioblastoma cells. It also has potential for treating triple-negative breast cancer. The study highlights the diverse mechanisms of action of this complex.
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 that are able to create several therapeutic effects besides the inhibition of oestrogen receptor α (Erα). Drawing inspiration from tamoxifen metabolite structures (4-hydroxytamoxifen and 4,4’-dihyroxytamoxifen), wherein 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 like copper(II) dichloride, yielding [CuCl(ÎĽ-Cl)(L-Îş2N,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 in regards to challenging breast cancer subtypes.