Work

Stabilization of Telomere DNA, and Mechanism of Apoptosis of Tumor Cells Induced by Ruthenium Complexes

Year: 2014

Type: article

Abstract: Telomerase is highly expressed in tumor cells, which has become an important target of anticancer drugs.Since many tumor cells were rich in G4-DNA, we investigated the capabilities of these two ruthenium complexes to stabilize G4-DNA.Two ruthenium(II) complexes were synthesized and characterized via electrospray ionization-mass spectrometry.Since many tumor cells were rich in G4-DNA, we investigated the capabilities of these two ruthenium complexes to stabilize G4-DNA.The interactions of these compounds with G-quadruplex DNA have been studied by fluorescence spectroscopy and circular dichroism (CD) spectroscopy.The stabilization of quadruplex DNA to complex 2 was better than complex 1, and complex 2 can induce telomeric G-quadruplex to occur conformation transformation, while complex 1 cannot.The results showed that the interaction of ruthenium complexes with G-quadruplex DNA was related with the plane of ligand.A novel visual method has been developed for making a distinction between ct-DNA and HTG21 by our Ru complexes binding hemin to form the hemin-G-quadruplex DNAzyme.The results showed that in the presence of complex 1 or 2, HTG21 can fold into a G-quadruplex, but CT-DNA cannot form the G-quadruplex structure.The anticancer activities of these complexes were evaluated by using the MTT assay.Interestingly, the anti-tumor activity of complex 2 exhibited greater inhibition to HepG2 cells, suggesting the ruthenium complexes were much less toxic towards normal cells, and speculated that it targeted the telomeric G-quadruplex was play a role on anti-tumor effect.To further evaluate the characteristics of the death induced by complexes 1 and 2-treated cells staining with Hoechst is analyzed by fluorescence microscopy.These results indicated that complex 2 revealed antiproliferative activities by apoptosis.We also used PI staining and flow cytometry to assess whether the ruthenium complex 2 affected cell cycle progression in HepG2 cells.Complex 2 is a potential antitumor drugs that can induce cancer cell death by acting on cell cycle arrest in G1 phase and the formation of DNA fragments (apoptosis characteristics).

Source: 化学学报

DOI: 10.6023/a13101092