C-Geranylated flavanone diplacone enhances in vitro antiproliferative and anti-inflammatory effects in its copper(II) complexes.
J Inorg Biochem
; 258: 112639, 2024 Sep.
Article
in En
| MEDLINE
| ID: mdl-38880070
ABSTRACT
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]â
2H2O (1) and {[Cu(phen)(H2dipl)2]â
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.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Copper
/
Flavanones
/
Cell Proliferation
/
Coordination Complexes
/
Antineoplastic Agents
Limits:
Humans
Language:
En
Journal:
J Inorg Biochem
Year:
2024
Document type:
Article
Country of publication:
United States