Arene Ru(II) Complexes Acted as Potential KRAS G-Quadruplex DNA Stabilizer Induced DNA Damage Mediated Apoptosis to Inhibit Breast Cancer Progress

Abstract

A series of arene Ru(II) complexes, [(η6-MeC6H5)Ru(L)Cl]Cl, (L=o-ClPIP, 1; m-ClPIP, 2 and p-ClPIP, 3) (o-ClPIP=2-(2-chlorophenyl)imidazo[4,5-f][1,10]phenanthroline; m-ClPIP=2-(3-chlorophenyl)imidazo[4,5-f][1,10]phenanthroline; p-ClPIP=2-(4-chlorophenyl)imidazo[4,5-f][1,10]phenanthroline) was synthesized and investigated as a potential apoptosis inducer in chemotherapy. Spectroscopy and molecular docking simulations show that 1 exhibits moderated binding affinity to KRAS G-quadruplex DNA by groove mode. Further, in vitro studies reveal that 1 displays inhibitory activity against MCF-7 growth with IC50 = 3.7 ± 0.2 μM. Flow cytometric analysis, comet assay, and immunofluorescence confirm that 1 can induce the apoptosis of MCF-7 cells and G0/G1 phase arrest through DNA damage. In summary, the prepared arene Ru(II) complexes can be developed as a promising candidate for targeting G-quadruplex structure to induce the apoptosis of breast cancer cells via binding and stabilizing KRAS G-quadruplex conformation on oncogene promoter.

Anticancer activity and morphological analysis of Pt (II) complexes: Their DFT approach, docking simulation, and ADME‐Tox profiling

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Selective Targeting of Regulated Rhabdomyosarcoma Cells by Trinuclear Ruthenium(II)–Arene Complexes

“…Given that 1 shows potent cytotoxicity and ruthenium­(II) arene complexes are generally known to induce DNA damage leading to cell death, the ability of 1 to induce DNA damage was studied by monitoring the levels of γH2AX, a protein related to the DNA damage pathway. − The levels of γH2AX, a robust marker for DNA double-strand breaks, were markedly increased in a dose-dependent manner in both RMS cell lines (Figure a) indicating that 1 indeed induces DNA damage.…”

Piano-stool ruthenium(ii) complexes with maleimide and phosphine or phosphite ligands: synthesis and activity against normal and cancer cells

“…7 Arene ruthenium( ii ) complex leads to a significant increase of apoptosis in MCF-7 cells, which is related to high genotoxicity displayed by severe DNA damage. 53 Ruthenium( ii )/allopurinol complex induced apoptosis in murine breast cancer cells by pro-caspase activation resulting in releasing of caspase 3 and 7 and Becklin-1 cleavage. 54 Ruthenium( ii ) complex with lapachol induced reactive oxygen species (ROS)-mediated apoptosis in DU-145 cells.…”