PMID- 24991692 OWN - NLM STAT- MEDLINE DCOM- 20150330 LR - 20140804 IS - 1873-3344 (Electronic) IS - 0162-0134 (Linking) VI - 139 DP - 2014 Oct TI - A monofunctional trinuclear platinum complex with steric hindrance demonstrates strong cytotoxicity against tumor cells. PG - 77-84 LID - S0162-0134(14)00167-6 [pii] LID - 10.1016/j.jinorgbio.2014.06.006 [doi] AB - Polynuclear platinum complexes constitute a special class of hopeful antitumor agents. In this study, a Y-type monofunctional trinuclear platinum complex (MTPC) with 1,3,5-tris(pyridin-2-ylmethoxy)benzene, ammine and chloride as ligands was synthesized and characterized by (1)H NMR and electrospray ionization mass spectrometry (ESI-MS). The DNA binding mode of MTPC was investigated using circular dichroism spectroscopy and gel electrophoresis, and the reactivity of MTPC towards glutathione was studied by (1)H NMR and ESI-MS. The results show that MTPC can affect the conformation of calf-thymus DNA (CT-DNA) significantly and tends to form 1,4-GG rather than 1,2-GG intrastrand crosslinks, which are different from the instance of cisplatin. MTPC reacts with glutathione quite slowly in comparison with cisplatin because of the steric hindrance. The cytotoxicity of MTPC was tested on the human breast cancer cell line MCF-7, the human non-small-cell lung cancer cell line A549, and the human ovarian cancer cell line Skov-3 by the MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] assay. MTPC is more potent than or comparable to cisplatin. The cellular inhibition mode of MTPC was examined by flow cytometry using MCF-7 cells. MTPC arrests the cell cycle mainly in G2 or M phase, while cisplatin arrests the cell cycle in S phase. Similar to cisplatin, MTPC kills the cells predominantly through an apoptotic pathway. CI - Copyright (c) 2014 Elsevier Inc. All rights reserved. FAU - Wu, Shangnong AU - Wu S AD - State Key Laboratory of Coordination Chemistry, School of Chemistry and Chemical Engineering, Nanjing University, Nanjing 210093, PR China. FAU - Wang, Xiaoyong AU - Wang X AD - State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, Nanjing 210093, PR China; State Key Laboratory of Analytical Chemistry for Life Science, Nanjing University, Nanjing 210093, PR China. Electronic address: boxwxy@nju.edu.cn. FAU - He, Yafeng AU - He Y AD - State Key Laboratory of Coordination Chemistry, School of Chemistry and Chemical Engineering, Nanjing University, Nanjing 210093, PR China. FAU - Zhu, Zhenzhu AU - Zhu Z AD - State Key Laboratory of Coordination Chemistry, School of Chemistry and Chemical Engineering, Nanjing University, Nanjing 210093, PR China. FAU - Zhu, Chengcheng AU - Zhu C AD - State Key Laboratory of Coordination Chemistry, School of Chemistry and Chemical Engineering, Nanjing University, Nanjing 210093, PR China. FAU - Guo, Zijian AU - Guo Z AD - State Key Laboratory of Coordination Chemistry, School of Chemistry and Chemical Engineering, Nanjing University, Nanjing 210093, PR China. Electronic address: zguo@nju.edu.cn. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20140617 PL - United States TA - J Inorg Biochem JT - Journal of inorganic biochemistry JID - 7905788 RN - 0 (Antineoplastic Agents) RN - 0 (Coordination Complexes) RN - 0 (Platinum Compounds) RN - 49DFR088MY (Platinum) RN - 9007-49-2 (DNA) RN - 91080-16-9 (calf thymus DNA) RN - GAN16C9B8O (Glutathione) SB - IM MH - Antineoplastic Agents/chemistry/*pharmacology MH - Apoptosis MH - Base Sequence MH - Cell Cycle Checkpoints MH - Coordination Complexes/chemistry/*pharmacology MH - DNA/chemistry MH - Glutathione/chemistry MH - Humans MH - MCF-7 Cells MH - Platinum/chemistry MH - Platinum Compounds/chemistry/*pharmacology OTO - NOTNLM OT - Antitumor drug OT - Apoptosis OT - DNA binding OT - Glutathione OT - Polynuclear platinum complex EDAT- 2014/07/06 06:00 MHDA- 2015/03/31 06:00 CRDT- 2014/07/04 06:00 PHST- 2014/03/17 00:00 [received] PHST- 2014/06/05 00:00 [revised] PHST- 2014/06/08 00:00 [accepted] PHST- 2014/07/04 06:00 [entrez] PHST- 2014/07/06 06:00 [pubmed] PHST- 2015/03/31 06:00 [medline] AID - S0162-0134(14)00167-6 [pii] AID - 10.1016/j.jinorgbio.2014.06.006 [doi] PST - ppublish SO - J Inorg Biochem. 2014 Oct;139:77-84. doi: 10.1016/j.jinorgbio.2014.06.006. Epub 2014 Jun 17.