C-Geranylated flavanone diplacone enhances in vitro antiproliferative and anti-inflammatory effects in its copper(II) complexes
| Autoři | |
|---|---|
| Rok publikování | 2024 |
| Druh | Článek v odborném periodiku |
| Časopis / Zdroj | Journal of Inorganic Biochemistry |
| Fakulta / Pracoviště MU | |
| Citace | |
| www | https://www.sciencedirect.com/science/article/pii/S0162013424001636?via%3Dihub |
| Doi | http://dx.doi.org/10.1016/j.jinorgbio.2024.112639 |
| Klíčová slova | Anti-cancer; Cellular effects; Copper(II); Diplacone; Inflammation; In vitro cytotoxicity |
| Popis | 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]& sdot;2H2O (1) and {[Cu(phen)(H2dipl)2]& sdot;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 approximate to 0.4-1.2 mu M), human lung carcinoma (A549, with IC50 approximate to 2 mu M) and osteosarcoma (HOS, with IC50 approximate to 3 mu M). 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-kappa B inhibition. As for the effects on PPAR alpha and/or PPAR gamma, 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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