CONICET | Buscador de Institutos y Recursos Humanos

Objective: Many flavonoids are natural chelators and flavonoid-metal complexes have shown to possess significant cytotoxicactivity. Chrysin is a flavone distributed in plants which was reportedto have many biological activities. In this study, a complex of chrysinwith magnesium(II) (Mgchrys) was synthesized and its anticancerand antimetastatic activity on A549 cell line were determined.Methods: Mgchrys has been synthesized in ethanol at pH=9 andcharacterized by spectroscopy techniques, elemental and thermogravimetricanalysis. The effect of the compounds on the humanlung cancer cell line (A549) viability was measured (MTT assay).The study on the normal lung epithelial cell line (MRC-5) was included.The morphological changes and intracellular ROS (reactiveoxygen species) content (using CM-H2DCFDA probe) were evaluated.In addition, the effect of the compounds at non-cytotoxic concentrationson adhesion, migration and invasion was investigated.Results: The IC50 values of chrysin were determined to be >100,66.4±4.2 and 37.3±3,3 μM at 24, 48 and 72 h, respectively. Mgchrysimproved the action of the free ligand being its IC50 values 83.9±2.9,28.2±3.5 and 21.1±3,2 μM at the same time. Ligand and complexdid not behave like cytotoxic agents in the normal cell line. Oxidativestress is the probable mechanism of action because the compoundsincreased levels of ROS. Some morphological changes (incrementof cytoplasm condensation, presence of pycnotic nuclei) were observedwhen the cells were incubated with Mgchrys. The adhesionto fibronectin ability of A549 cells treated with Mgchrys decreased 40% in comparison with the control. Chrysin and MgCl2 did not affectadhesion. Mgchrys showed significant inhibition of migration (45%)as compared to the ligand (16%). A 47% reduction on cell invasionwas observed when cells were treated with Mgchrys.Conclusion: This study shows that Mgchrys could be consideredas a promising chemotherapeutic agent.