Issue 11, 2013

Studies of ruthenium(ii)-2,2′-bisimidazole complexes on binding to G-quadruplex DNA and inducing apoptosis in HeLa cells

Abstract

Three ruthenium(II) complexes [Ru(bpy)2(biim)]2+ (1), [Ru(phen)2(biim)]2+ (2) and [Ru(p-mopip)2-(biim)]2+ (3) (where bpy is 2,2′-bipyridine, phen is 1,10-phenanthroline, biim is 2,2′-bisimidazole and p-mopip is 2-(4-methoxyphenyl)-imidazo-[4,5f]phenanthroline), have been synthesized and characterized. The interactions of human telomeric DNA oligomers 5′-G3(T2AG3)3-3′ (HTG21) with ruthenium(II) complexes were investigated via UV-vis, fluorescence resonance energy transfer (FRET) melting assay, polymerase chain reaction (PCR) stop assay, and circular dichroism (CD) measurements. The results indicated that the three ruthenium(II) complexes could stabilize the formation of human telomeric G-quadruplex DNA, and complex 2 was found to be the most efficient. In vitro cytotoxicity assay by MTT also showed that complex 2 was superior to complexes 1 and 3 in inhibiting the growth of cancer cells. Telomeric repeat amplification protocol (TRAP) showed that complexes 2 and 3 led to an inhibition of the telomerase activity, and complex 2 was the significantly better inhibitor. Flow cytometric analysis and evaluation of mitochondrial membrane potential demonstrated that complex 2 inhibited the growth of HeLa cells through induction of apoptotic cell death, as evidenced by the depletion of mitochondrial membrane potential in HeLa cells.

Graphical abstract: Studies of ruthenium(ii)-2,2′-bisimidazole complexes on binding to G-quadruplex DNA and inducing apoptosis in HeLa cells

Supplementary files

Article information

Article type
Paper
Submitted
22 May 2013
Accepted
21 Aug 2013
First published
22 Aug 2013

New J. Chem., 2013,37, 3706-3715

Studies of ruthenium(II)-2,2′-bisimidazole complexes on binding to G-quadruplex DNA and inducing apoptosis in HeLa cells

Y. Xia, Q. Chen, X. Qin, D. Sun, J. Zhang and J. Liu, New J. Chem., 2013, 37, 3706 DOI: 10.1039/C3NJ00542A

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