title: Synthesis, characterization, DNA interaction, antioxidant and anticancer activity studies of ruthenium(II) polypyridyl complexes.
abstract: Two new Ru(II) polypyridyl complexes [Ru(phen)₂(adppz)](ClO₄)₂ (1) and [Ru(dip)₂(adppz)](ClO₄)₂ (2) have been synthesized and characterized. The DNA-binding constants were determined to be 6.54 ± 0.42 × 10(5) and 7.65 ± 0.20 × 10(5)M(-1) for complexes 1 and 2. DNA binding experiments indicated that complexes 1 and 2 interact with DNA through intercalative mode. Antioxidant activity shows that the complexes have significant hydroxyl radical scavenging activity. Cytotoxic activities suggest that the complex 2 exhibits higher cytotoxic activity against BEL-7402, MG-63 and SKBR-3 cells than complex 1 under identical conditions. Complexes 1 and 2 can induce apoptosis of BEl-7402 cells. We have identified several cellular mechanisms induced by 1 and 2 in BEL-7402 cells, including the level detection of ROS, activation of procaspase 3, caspase 7, the expression of antiapoptotic proteins Bcl-x, Bcl-2, proapoptotic proteins Bad, Bax, Bid and cell cycle arrest. Thus, complexes 1 and 2 inhibit growth of BEL-7402 cells through induction of apoptotic cell death, enhancement of ROS levels and S-phase and G0/G1 cell cycle arrest. Further investigations have shown that complex 2 induces apoptosis by regulating the expression of Bcl-2 family proteins.
authors.affiliation: School of Pharmacy, Guangdong Pharmaceutical University, Guangzhou 510006, PR China.
authors.forename: Guang-Bin
authors.initials: GB
authors.lastname: Jiang
authors.forename: Yang-Yin
authors.initials: YY
authors.lastname: Xie
authors.forename: Gan-Jian
authors.initials: GJ
authors.lastname: Lin
authors.forename: Hong-Liang
authors.initials: HL
authors.lastname: Huang
authors.forename: Zhen-Hua
authors.initials: ZH
authors.lastname: Liang
authors.forename: Yun-Jun
authors.initials: YJ
authors.lastname: Liu
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000378:metabolism / Q000494:pharmacology; D000975:Antioxidants / Q000138:chemical synthesis / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D053148:Caspase 3 / Q000378:metabolism; D053179:Caspase 7 / Q000378:metabolism; D059447:Cell Cycle Checkpoints / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D056831:Coordination Complexes / Q000138:chemical synthesis* / Q000378:metabolism / Q000494:pharmacology*; D004247:DNA / Q000737:chemistry / Q000378:metabolism*; D006801:Humans; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D012428:Ruthenium / Q000737:chemistry*
chemical_list: D000970:Antineoplastic Agents; D000975:Antioxidants; D056831:Coordination Complexes; D019253:Proto-Oncogene Proteins c-bcl-2; D017382:Reactive Oxygen Species; D012428:Ruthenium; D004247:DNA; D053148:Caspase 3; D053179:Caspase 7
keywords: Cell cycle arrest; Cytotoxicity in vitro; DNA-binding; Reactive oxygen species; Ru(II) polypyridyl complex; Western blot