title: Targeting nucleus DNA with a cyclometalated dipyridophenazineruthenium(II) complex.
abstract: Recently, coordinatively saturated and substitutionally inert Ru(II) complexes have been investigated as anticancer agents. Herein a cyclometalated Ru(II) complex, [Ru(bpy)(phpy)(dppz)](+), was found to be rapidly taken up by cancer cells, and nearly 90% of the complex accumulated in the nuclei of cancer cells after a 2 h incubation. The anticancer activity of this complex was screened against a panel of cancer cell lines. Remarkably, it exhibited IC50 values that were an order of magnitude lower than those of cisplatin. This complex also displayed potencies superior to those of cisplatin against 3D tumor spheroids. Further studies revealed that the high DNA binding affinity of [Ru(bpy)(phpy)(dppz)](+) resulted in effective disruption of the binding of transcription factor NF-κB to DNA sequences, thereby inhibiting cellular transcription and leading to irreversible cancer cell apoptosis. Our work provides new insights into understanding the biological interactions and anticancer molecular mechanisms of DNA-specific Ru(II) polypyridyl complexes.
authors.affiliation: MOE Key Laboratory of Bioinorganic and Synthetic Chemistry, State Key Laboratory of Optoelectronic Materials and Technologies, School of Chemistry and Chemical Engineering, Sun Yat-Sen University , Guangzhou, 510275, China.
authors.forename: Huaiyi
authors.initials: H
authors.lastname: Huang
authors.forename: Pingyu
authors.initials: P
authors.lastname: Zhang
authors.forename: Bole
authors.initials: B
authors.lastname: Yu
authors.forename: Yu
authors.initials: Y
authors.lastname: Chen
authors.forename: Jinquan
authors.initials: J
authors.lastname: Wang
authors.forename: Liangnian
authors.initials: L
authors.lastname: Ji
authors.forename: Hui
authors.initials: H
authors.lastname: Chao
mesh_terms: D000970:Antineoplastic Agents / Q000378:metabolism* / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D045744:Cell Line, Tumor; D002467:Cell Nucleus / Q000378:metabolism*; D002945:Cisplatin; D056831:Coordination Complexes / Q000138:chemical synthesis* / Q000378:metabolism; D004273:DNA, Neoplasm / Q000737:chemistry* / Q000378:metabolism; D005260:Female; D006801:Humans; D020128:Inhibitory Concentration 50; D008297:Male; D016328:NF-kappa B / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; D056831:Coordination Complexes; D004273:DNA, Neoplasm; D016328:NF-kappa B; D002945:Cisplatin