RESUMO
Four neutral Rh1-Rh4 complexes of the general formula [Rh2(CH3COO)4L2], where L is an N-alkylimidazole ligand, were synthesized and characterized using various spectroscopic techniques, and in the case of Rh4 the crystal structure was confirmed. Investigation of the interactions of these complexes with HSA by fluorescence spectroscopy revealed that the binding constants Kb are moderately strong (â¼104 M-1), and site-marker competition experiments showed that the complexes bind to Heme site III (subdomain IB). Competitive binding studies for CT DNA using EB and HOE showed that the complexes bind to the minor groove, which was also confirmed by viscosity experiments. Molecular docking confirmed the experimental data for HSA and CT DNA. Antimicrobial tests showed that the Rh2-Rh4 complexes exerted a strong inhibitory effect on G+ bacteria B. cereus and G- bacteria V. parahaemolyticus as well as on the yeast C. tropicalis, which showed a higher sensitivity compared to fluconazole. The cytotoxic activity of Rh1-Rh4 complexes tested on three cancer cell lines (HeLa, HCT116 and MDA-MB-231) and on healthy MRC-5 cells showed that all investigated complexes elicited more efficient cytotoxicity on all tested tumor cells than on control cells. Investigation of the mechanism of action revealed that the Rh1-Rh4 complexes inhibit cell proliferation via different mechanisms of action, namely apoptosis (increase in expression of the pro-apoptotic Bax protein and caspase-3 protein in HeLa and HCT116 cells; changes in mitochondrial potential and mitochondrial damage; release of cytochrome c from the mitochondria; cell cycle arrest in G2/M phase in both HeLa and HCT116 cells together with a decrease in the expression of cyclin A and cyclin B) and autophagy (reduction in the expression of the protein p62 in HeLa and HCT116 cells).
Assuntos
Antineoplásicos , Apoptose , Complexos de Coordenação , Ródio , Humanos , Antineoplásicos/farmacologia , Antineoplásicos/química , Antineoplásicos/síntese química , Complexos de Coordenação/farmacologia , Complexos de Coordenação/química , Complexos de Coordenação/síntese química , Apoptose/efeitos dos fármacos , Ródio/química , Ródio/farmacologia , Simulação de Acoplamento Molecular , Anti-Infecciosos/farmacologia , Anti-Infecciosos/química , Anti-Infecciosos/síntese química , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Testes de Sensibilidade Microbiana , Candida tropicalis/efeitos dos fármacos , Ensaios de Seleção de Medicamentos Antitumorais , Antibacterianos/farmacologia , Antibacterianos/química , Antibacterianos/síntese química , Células HeLaRESUMO
PURPOSE: The treatment options of endometrial hyperplasia consist of surgical, interventional and medical therapies including apoptosis-inducing agents. The purpose of the study was to evaluate the effects of ultraviolet (UV) radiation on the viability and the type of cell death on the human endometrial stromal cells (ThESC) line. METHODS: We investigated the effect of UV exposure on human endometrial stromal cell line (ThESC) on cell viability using MTT assay as well as changes in cell morphology using phase microscopy and acridine orange (AO)/ethidium bromide (EB) cell staining. RESULTS: UV treatment significantly decreased the percentage of the viable ThESC cells compared to the viability of untreated control cells using MTT assay (p<0.05). In addition, UV treatment of ThESC cells for 60 and 90 min induced high level of cell morphology disruption, followed with loss of both the cell shape and the presence of defragmented debris and stained with intense red color. CONCLUSIONS: The obtained results suggest the potential role of UV light application as additional treatment option of benign endometrium hyperplasia alone or in combination with other treatment modalities.
