Novel Copper(II) Complexes Containing β‑Diketones and Imines as Ligands Modulate the Expression of lncRNAs in Triple-Negative Breast Cancer Cells

In this study, four
novel Cu(II) complexes of the type [Cu(imine)(b-diketone)(NO3)], namely, [Cu(clmp)(bta)(NO3)]·H2O 1, [Cu(clmp)(btacl)(NO3)] 2, [Cu(memp)(bta)(NO3)]·H2O 3, and [Cu(memp)(btacl)(NO3)]·H2O 4, in which clmp = 4-chloro-N-(pyridin-2-methylene)
aniline, memp = 4-methyl-N-(pyridin-2-methylene)
aniline, bta = (4,4,4-trifluoro-1-phenyl-1,3-butanedionate, and btacl
= 1-(4-chlorophenyl)-4,4,4-trifluoro-1,3-butanedionate), were prepared
and characterized by elemental analysis, mass spectrometry, conductivity
measurements, FT-IR, UV–vis, and single-crystal X-ray diffraction.
The spectral and structural data confirmed that the β-diketone
anions coordinate to Cu(II) via the oxygen atoms, while the imine
ligands coordinate by the nitrogen atoms. A weakly coordinated nitrate
completes the coordination sphere around the metal center. Subsequently, in vitro experiments were conducted in MDA-MB231 triple-negative
breast cancer cells (TNBC) in which MTT, SRB, LDH, clonogenicity,
migration, and caspase activity analyses were performed. lncRNAs associated
with epithelial-mesenchymal transition (EMT) were also quantified
by qPCR. In the MTT assay, complexes 2 and 3 exhibited IC50 values below 20 μM and greater selectivity
toward the nontumorigenic MCF-10A cells. The SRB and LDH assays also
demonstrated reduced cell viability and increased lactate dehydrogenase
release mediated by both complexes. Clonogenicity and migration of
TNBC cells were also reduced by 2 and 3,
and an increase in the activity of caspases 3 and 8 was observed,
with the most pronounced effects recorded for 3. Finally,
the expression of lncRNAs was downregulated by 2 and 3, demonstrating the role of the complexes in the modulation
of EMT. These findings highlight complexes 2 and 3 as potential antitumor agents for TNBC, emphasizing the
importance of exploring the intrinsic mechanisms underlying their
anticancer activity.