PMID- 27816647 OWN - NLM STAT- MEDLINE DCOM- 20170328 LR - 20170328 IS - 1873-2682 (Electronic) IS - 1011-1344 (Linking) VI - 165 DP - 2016 Dec TI - Synthesis, characterization and anticancer effect of the ruthenium (II) polypyridyl complexes on HepG2 cells. PG - 246-255 LID - S1011-1344(16)30844-2 [pii] LID - 10.1016/j.jphotobiol.2016.10.038 [doi] AB - As one of the major cell regulated center, mitochondria are closely associated with cell proliferation, apoptosis of tumor cell. In this work, four new ruthenium (II) polypyridyl complexes [Ru(bpy)(2)(FTTP)](ClO(4))(2) (1) (FTTP=11-(3-fluoro-naphthalen-2-yloxy)-4,5,9,14-tetraaza-benzo[b]triphenylene, bpy=2,2'-bipyridine), [Ru(phen)(2)(FTTP)](ClO(4))(2) (2) (phen=1,10-phenanthroline), [Ru(bpy)(2)(PTTP)](ClO(4))(2) (3) (PTTP=2-phenoxy-1,4,8,9-tetraazatriphenylene) and [Ru(phen)(2)(PTTP)](ClO(4))(2) (4) were synthesized and characterized by elemental analysis, ESI-MS, (1)H NMR and (13)C NMR. The cytotoxic activity, ability of inhibiting cell invasion, cell cycle arrest and apoptosis-inducing mechanism of these Ru(II) complexes have been investigated in detail by MTT (3-(4,5-dimethylthiazole)-2,5-diphenyltetrazolium bromide) method, invasion assay, comet assay as well as western blotting techniques. Notably, complexes 1-4 displayed high cytotoxic activity against liver carcinoma HepG2 cells and the IC(50) values of complexes 1-4 against HepG2 cells are 10.4+/-1.2, 9.3+/-0.6, 29.1+/-1.5 and 5.6+/-1.2muM, respectively. The comet assay showed that the complexes can induce DNA damage. The acridine orange (AO) and ethidium bromide (EB) staining method indicated that the complexes can cause apoptosis in HepG2 cells. Further studies showed that complexes 1-4 caused cell cycle arrest at G0/G1 phase and induced HepG2 cells apoptosis through a ROS-mediated mitochondrial dysfunction pathway, which involved an increase in the levels of reactive oxygen species (ROS), a decrease in the mitochondrial membrane potential, activation of caspases and Bcl-2 family proteins. CI - Copyright A(c) 2016 Elsevier B.V. All rights reserved. FAU - Wan, Dan AU - Wan D 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 - Yang, Hui-Hui AU - Yang HH AD - School of Pharmacy, Guangdong Pharmaceutical University, Guangzhou 510006, PR China. FAU - Tang, Bing AU - Tang B 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 - Zeng, Chuan-Chuan AU - Zeng CC 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; Guangdong Cosmetics Engineering & Technology Research Center, Guangzhou 510006, PR China. Electronic address: lyjche@163.com. LA - eng PT - Journal Article DEP - 20161031 PL - Switzerland TA - J Photochem Photobiol B JT - Journal of photochemistry and photobiology. B, Biology JID - 8804966 RN - 0 (Pyridines) RN - 0 (Reactive Oxygen Species) RN - 7UI0TKC3U5 (Ruthenium) SB - IM MH - Apoptosis MH - Carbon-13 Magnetic Resonance Spectroscopy MH - DNA Damage MH - Hep G2 Cells MH - Humans MH - Membrane Potential, Mitochondrial MH - Proton Magnetic Resonance Spectroscopy MH - Pyridines/*chemistry MH - Reactive Oxygen Species/metabolism MH - Ruthenium/*chemistry MH - Spectrometry, Mass, Electrospray Ionization MH - Spectrophotometry, Ultraviolet OTO - NOTNLM OT - Cell invasion OT - Cytotoxicity in vitro OT - Mitochondrial membrane potential OT - Reactive oxygen species OT - Ruthenium (II) polypyridyl complexes OT - Western blot analysis EDAT- 2016/11/07 06:00 MHDA- 2017/03/30 06:00 CRDT- 2016/11/07 06:00 PHST- 2016/09/25 00:00 [received] PHST- 2016/10/27 00:00 [accepted] PHST- 2016/11/07 06:00 [pubmed] PHST- 2017/03/30 06:00 [medline] PHST- 2016/11/07 06:00 [entrez] AID - S1011-1344(16)30844-2 [pii] AID - 10.1016/j.jphotobiol.2016.10.038 [doi] PST - ppublish SO - J Photochem Photobiol B. 2016 Dec;165:246-255. doi: 10.1016/j.jphotobiol.2016.10.038. Epub 2016 Oct 31.