C-Geranylated flavanone diplacone enhances in vitro antiproliferative and anti-inflammatory effects in its copper(II) complexes
Language English Country United States Media print-electronic
Document type Journal Article, Research Support, Non-U.S. Gov't
Grant support
I 5215
Austrian Science Fund FWF - Austria
PubMed
38880070
DOI
10.1016/j.jinorgbio.2024.112639
PII: S0162-0134(24)00163-6
Knihovny.cz E-resources
- Keywords
- Anti-cancer, Cellular effects, Copper(II), Diplacone, In vitro cytotoxicity, Inflammation,
- MeSH
- Anti-Inflammatory Agents pharmacology chemistry MeSH
- Autophagy drug effects MeSH
- Flavanones * pharmacology chemistry MeSH
- Coordination Complexes * pharmacology chemical synthesis chemistry MeSH
- Humans MeSH
- Copper * chemistry pharmacology MeSH
- Cell Line, Tumor MeSH
- Cell Proliferation * drug effects MeSH
- Antineoplastic Agents * pharmacology chemistry chemical synthesis MeSH
- Reactive Oxygen Species metabolism MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Names of Substances
- Anti-Inflammatory Agents MeSH
- Flavanones * MeSH
- Coordination Complexes * MeSH
- Copper * MeSH
- Antineoplastic Agents * MeSH
- Reactive Oxygen Species MeSH
Two copper(II) complexes containing diplacone (H4dipl), a naturally occurring C-geranylated flavanone derivative, in combination with bathophenanthroline (bphen) or 1,10-phenanthroline (phen) with the composition [Cu3(bphen)3(Hdipl)2]⋅2H2O (1) and {[Cu(phen)(H2dipl)2]⋅1.25H2O}n (2) were prepared and characterized. As compared to diplacone, the complexes enhanced in vitro cytotoxicity against A2780 and A2780R human ovarian cancer cells (IC50 ≈ 0.4-1.2 μM), human lung carcinoma (A549, with IC50 ≈ 2 μM) and osteosarcoma (HOS, with IC50 ≈ 3 μM). Cellular effects of the complexes in A2780 cells were studied using flow cytometry, covering studies concerning cell-cycle arrest, induction of cell death and autophagy and induction of intracellular ROS/superoxide production. These results uncovered a possible mechanism of action characterized by the G2/M cell cycle arrest. The studies on human endothelial cells revealed that complexes 1 and 2, as well as their parental compound diplacone, do possess anti-inflammatory activity in terms of NF-κB inhibition. As for the effects on PPARα and/or PPARγ, complex 2 reduced the expression of leukocyte adhesion molecules VCAM-1 and E-selectin suggesting its dual anti-inflammatory capacity. A wide variety of Cu-containing coordination species and free diplacone ligand were proved by mass spectrometry studies in water-containing media, which might be responsible for multimodal effect of the complexes.
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