title: Ruthenium methylimidazole complexes induced apoptosis in lung cancer A549 cells through intrinsic mitochondrial pathway.
abstract: Ruthenium(II) methylimidazole complexes, with the general formula [Ru(MeIm)(4)(N⌢N)](2+) (N⌢N = tip (RMC1), iip (RMC2), dppz (RMC3), dpq (RMC4); MeIm = 1-methylimidazole, tip = 2-(thiophene-2-yl)-1H-imidazo [4,5-f] [1,10]phenanthroline, iip = 2-(1H-imidazol-4-yl)-1H-imidazo [4,5-f] [1,10]phenanthroline, dppz = dipyrido[3,2-a:2',3'-c]phenazine, dpq = pyrazino [2,3-f] [1,10]phenanthroline), were synthesized and characterized. As determined by MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay, these complexes displayed potent anti-proliferation activity against various cancer cells. RMC1 inhibited the growth of A549 (human lung adenocarcinoma) lung cells through induction of apoptotic cell death, as evidenced by the accumulation of cell population in sub-G1 phase. RMC1 also induced the depletion of mitochondrial membrane potential in A549 cells by regulating the expression of pro-survival and pro-apoptotic Bcl-2 family members. Another experiment showed that Bid protein was also activated by RMC1, which implied that RMC1 could existed two pathways crosstalk, namely, have exogenous death receptor signaling pathway. These results demonstrated that RMC1 induced cancer cell death by acting on both mitochondrial and death receptor apoptotic pathways, suggesting that RMC1 could be a candidate for further evaluation as a chemotherapeutic agent against human cancers.
authors.affiliation: Department of Chemistry, Jinan University, Guangzhou 510632, China.
authors.forename: Xiaoxin
authors.initials: X
authors.lastname: Yang
authors.forename: Lanmei
authors.initials: L
authors.lastname: Chen
authors.forename: Yanan
authors.initials: Y
authors.lastname: Liu
authors.forename: Yongguang
authors.initials: Y
authors.lastname: Yang
authors.forename: Tianfeng
authors.initials: T
authors.lastname: Chen
authors.forename: Wenjie
authors.initials: W
authors.lastname: Zheng
authors.forename: Jie
authors.initials: J
authors.lastname: Liu
authors.forename: Qing-Yu
authors.initials: QY
authors.lastname: He
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D000077192:Adenocarcinoma of Lung; D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D053148:Caspase 3 / Q000235:genetics / Q000378:metabolism; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D056831:Coordination Complexes / Q000138:chemical synthesis / Q000494:pharmacology*; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D007093:Imidazoles / Q000737:chemistry*; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D008928:Mitochondria / Q000187:drug effects* / Q000378:metabolism; D010618:Phenanthrolines / Q000737:chemistry; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics / Q000378:metabolism; D012428:Ruthenium / Q000737:chemistry*; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D000970:Antineoplastic Agents; D056831:Coordination Complexes; D007093:Imidazoles; D010618:Phenanthrolines; D019253:Proto-Oncogene Proteins c-bcl-2; D012428:Ruthenium; D053148:Caspase 3