Biology subjects

Facchin, G.

Publications and source records attributed to Facchin, G..

3 recordsLinked to original sources

bioRxiv2026

Methyl-substituted 1,10-phenanthroline derivatives in copper(II) complexes enhance antitumor activity and inhibit NHE1 in MDA-MB-231 breast cancer cells

Three copper(II) complexes containing 1,10-phenanthroline derivatives, [CuCl2(phen)].0.5H2O (1), [CuCl2(neo)].0.75H2O (2), and [CuCl2(tmp)].H2O (3), were evaluated for their antitumor activity in MDA-MB-231 breast cancer cells. All complexes markedly reduced cell viability, exhibiting significantly lower IC values and higher selectivity indices than the corresponding free ligands, CuCl2, and cisplatin, highlighting the therapeutic advantage of metal complexation. Among them, only 1 induced DNA damage at sub-IC concentrations. Cytotoxicity in all complexes was associated with intracellular ROS generation and apoptosis, although 2 and 3 produced a stronger oxidative response. Complex 3 additionally promoted necrosis. Cell proliferation was inhibited in a concentration-dependent manner, accompanied by increased intracellular copper accumulation. Moreover, 2 and 3 significantly inhibited Na/H exchanger 1 (NHE1) activity, reducing cell migration and MMP-9 activity. Western blot analysis further demonstrated that all three complexes modulated the expression of NHE1, G protein-coupled estrogen receptor (GPER), and apoptosis-related proteins. Overall, our findings show that ligand methylation enhances the antitumor activity of copper(II) complexes and shifts their mechanism of action from DNA damage-driven cytotoxicity toward ROS-mediated apoptosis, while also improving inhibition of NHE1-dependent migratory pathways. These results identify NHE1 as a key molecular target underlying the enhanced antitumor activity of methylated phenanthroline copper(II) complexes.

cell biology↗

bioRxiv2024

Role of the NHE1 exchanger in the antitumor effects of copper(II) complexes and phenanthroline derivatives

Three copper(II) complexes containing 1,10-phenanthroline ([CuCl2(phen)]{middle dot}4H2O,1), neocuproine ([CuCl2(neo)]{middle dot}4H2O, 2) and tetramethyl-phenanthroline ([CuCl2(tmp)]{middle dot}4H2O, 3) as the primary ligand and another three copper(II) complexes with the L-Ala-Phe dipeptide as an auxiliary ligand: [Cu(L-Ala-Phe)(phen)]{middle dot}4H2O (4), [Cu(L-Ala-Phe)(neo)]{middle dot}4H2O (5) and [Cu(L-Ala-Phe)(tmp)]{middle dot}4H2O (6), inhibited cell viability in breast cancer MCF-7 cell line, both in the monolayer and spheroid cell culture models. The pair with tetramethyl-phenanthroline displayed a better selectivity index than cisPt and non-cytotoxicity-related ROS induction and apoptosis in the monolayer breast cancer model. Cell proliferation was affected by all compounds in a concentration-dependent manner, with a more substantial effect on the tetramethyl-phenanthroline complexes. Cell viability on multicellular spheroids showed a concentration-dependent reduction from 1 M, with IC50 that were half the one for cisplatin. All copper complexes, except for 1 showed DNA damage, demonstrated by the comet assay at a concentration below the IC50. The role of NHE1 has been linked to many types of cancers. Our study revealed that all compounds inhibited NHE1 activity in MCF-7 cells. However, only complexes containing the dipeptide auxiliary ligand could extend their effect on cell migration (Wound Healing Assay) and MMP-9 activity studied by zimography. Wester Blot analysis showed that expressions of MMP-2, MMP-9, and NHE1 were affected when MCF7 cells were treated with the six compounds as well. Overall, our results reveal an antitumor effect of all copper(II) complexes studied in breast cancer cells and a fundamental role of NHE1 in cell migration.

cancer biology↗

bioRxiv2020

Food for the Empire: dietary pattern of Imperial Rome inhabitants.

This paper aims to provide a broad diet reconstruction for people buried in archaeologically defined contexts in Rome (1st-3rd centuries CE), in order to combine archaeological and biological evidence focusing on dietary preferences in Imperial Rome. A sample of 214 human bones recovered from 6 funerary contexts were selected for carbon and nitrogen stable isotope analysis. The baseline for the terrestrial protein component of the diet was set using 17 coeval faunal remains recovered from excavations at Rome supplemented by previously published data for the same geographic and chronological frames. {delta}13C ranges from -19.95{per thousand} to -14.78{per thousand}, whereas {delta}15N values are between 7.17{per thousand} and 10.00{per thousand}. The values are consistent with an overall diet mainly based on terrestrial resources. All the human samples rely on a higher trophic level than the primary consumer faunal samples. Certainly, C3 plants played a pivotal role in the dietary habits. However, C4 plants also seem to have been consumed, albeit they were not as widespread and were not always used for human consumption. The environment played a critical role also for Romans of lower social classes. The topographical location determined the preferential consumption of food that people could obtain from their neighborhood.

evolutionary biology↗