PMID- 27288660 OWN - NLM STAT- MEDLINE DCOM- 20170313 LR - 20170313 IS - 1873-2682 (Electronic) IS - 1011-1344 (Linking) VI - 161 DP - 2016 Aug TI - Synthesis, characterization and anticancer activity studies of ruthenium(II) polypyridyl complexes on A549 cells. PG - 295-303 LID - S1011-1344(16)30179-8 [pii] LID - 10.1016/j.jphotobiol.2016.06.004 [doi] AB - Four new ruthenium(II) polypyridyl complexes [Ru(N-N)2(bddp)](ClO4)21-4 (N-N=dmb: 4,4'-dimethyl-2,2'-bipyridine 1, bpy: 2,2'-bipyridine 2, phen: 1,10-phenanthroline 3 and dmp: 2,9-dimethyl-1,10-phenanthroline 4, bddp=benzilo[2,3-b]-1,4-diazabenzo[i]dipyrido[3,2-a:2',3'-c]phenazine) were synthesized and characterized by elemental analysis, ESI-MS and (1)H NMR. The cytotoxicity in vitro of the complexes against BEL-7402, HeLa, MG-63 and A549 cell lines was investigated by MTT method. The complexes show high cytotoxic activity toward the selected cell lines with an IC50 value ranging from 5.3+/-0.6 to 15.7+/-3.6muM. The apoptosis was studied with acridine orange (AO)/ethdium bromide (EB) and Hoechst 33258 staining methods. The cellular uptake was investigated with DAPI staining method. The reactive oxygen species (ROS) and mitochondrial membrane potential were performed under fluorescent microscope and flow cytometry. The complexes can induce an increase in the ROS levels and a decrease in the mitochondrial membrane potential. The comet assay was studied with fluorescent microscope. The percentage in apoptotic and necrotic cells and cell cycle arrest were assayed by flow cytometry. The effects of the complexes on the expression of caspases and Bcl-2 family proteins were studied by western blot analysis. The results show that the complexes induce apoptosis in A549 cells through an ROS-mediated mitochondrial dysfunction pathway, which was accompanied by regulating the expression of Bcl-2 family proteins. CI - Copyright (c) 2016 Elsevier B.V. All rights reserved. FAU - Zeng, Chuan-Chuan AU - Zeng CC AD - School of Pharmacy, Guangdong Pharmaceutical University, Guangzhou 510006, PR China. FAU - Jiang, Guang-Bin AU - Jiang GB AD - School of Pharmacy, Guangdong Pharmaceutical University, Guangzhou 510006, PR China. FAU - Lai, Shang-Hai AU - Lai SH AD - School of Pharmacy, Guangdong Pharmaceutical University, Guangzhou 510006, PR China. FAU - Zhang, Cheng AU - Zhang C AD - School of Pharmacy, Guangdong Pharmaceutical University, Guangzhou 510006, PR China. FAU - Yin, Hui AU - Yin H AD - Department of Microbiology and Immunology, Guangdong Pharmaceutical University, Guangzhou 510006, PR China. Electronic address: huiyin0103@163.com. FAU - Tang, Bing AU - Tang B AD - School of Pharmacy, Guangdong Pharmaceutical University, Guangzhou 510006, PR China. FAU - Wan, Dan AU - Wan D AD - School of Pharmacy, Guangdong Pharmaceutical University, Guangzhou 510006, PR China. FAU - Liu, Yun-Jun AU - Liu YJ AD - School of Pharmacy, Guangdong Pharmaceutical University, Guangzhou 510006, PR China. Electronic address: lyjche@163.com. LA - eng PT - Journal Article DEP - 20160605 PL - Switzerland TA - J Photochem Photobiol B JT - Journal of photochemistry and photobiology. B, Biology JID - 8804966 RN - 0 (Antineoplastic Agents) RN - 0 (Coordination Complexes) RN - 0 (Proto-Oncogene Proteins c-bcl-2) RN - 0 (Reactive Oxygen Species) RN - 551W113ZEP (2,2'-Dipyridyl) RN - 7UI0TKC3U5 (Ruthenium) RN - EC 3.4.22.- (Caspases) SB - IM MH - 2,2'-Dipyridyl/chemistry MH - A549 Cells MH - Antineoplastic Agents/*chemical synthesis/chemistry/toxicity MH - Apoptosis/drug effects MH - Caspases/metabolism MH - Cell Cycle Checkpoints/drug effects MH - Cell Line, Tumor MH - Comet Assay MH - Coordination Complexes/*chemical synthesis/chemistry/toxicity MH - DNA Fragmentation/drug effects MH - HeLa Cells MH - Humans MH - Membrane Potential, Mitochondrial/drug effects MH - Microscopy, Fluorescence MH - Proto-Oncogene Proteins c-bcl-2/metabolism MH - Reactive Oxygen Species/metabolism MH - Ruthenium/*chemistry OTO - NOTNLM OT - Apoptosis OT - Cell cycle arrest OT - Cellular uptake OT - Ru(II) complex OT - Western blot analysis EDAT- 2016/06/12 06:00 MHDA- 2017/03/14 06:00 CRDT- 2016/06/12 06:00 PHST- 2016/03/18 00:00 [received] PHST- 2016/06/03 00:00 [revised] PHST- 2016/06/03 00:00 [accepted] PHST- 2016/06/12 06:00 [entrez] PHST- 2016/06/12 06:00 [pubmed] PHST- 2017/03/14 06:00 [medline] AID - S1011-1344(16)30179-8 [pii] AID - 10.1016/j.jphotobiol.2016.06.004 [doi] PST - ppublish SO - J Photochem Photobiol B. 2016 Aug;161:295-303. doi: 10.1016/j.jphotobiol.2016.06.004. Epub 2016 Jun 5.