PMID- 29202332 OWN - NLM STAT- MEDLINE DCOM- 20180614 LR - 20180705 IS - 1873-3344 (Electronic) IS - 0162-0134 (Linking) VI - 179 DP - 2018 Feb TI - Chloro(triphenylphosphine)gold(I) a forefront reagent in gold chemistry as apoptotic agent for cancer cells. PG - 107-120 LID - S0162-0134(17)30461-0 [pii] LID - 10.1016/j.jinorgbio.2017.11.004 [doi] AB - The antiproliferative activity of the gold complex [Au(tpp)Cl] (1) (tpp=triphenyphosphine) against human breast adenocarcinoma cells (MCF-7) and normal human fetal lung fibroblast cells (MRC-5) was investigated. The compound exhibits stronger activity against MCF-7 cells than cisplatin. The apoptotic pathway, especially though the mitochondrion damage was concluded by cell cycle arrest, flow cytometry using Annexin V-Fluorescein IsoThioCyanate (FITC) and Propidium Iodide (PI) as indicators, assays and permeabilization of the mitochondrial membrane tests. The molecular mechanism of action of 1 was further studied by: (i) its catalytic activity on the oxidation of linoleic acid (an acid that partakes in membrane fluidity) to hyperoxolinoleic acid by oxygen and (ii) its binding affinity towards the calf thymus (CT) DNA. Since the deactivation of cisplatin by glutathione (GSH), is related with the development of cell resistance, the reaction of 1 with GSH was investigated by UV absorption spectroscopy. The absence of micronucleus in cells confirms that the complex has no in vitro toxicity. The in vivo genotoxicity caused by 1 was evaluated by Allium cepa test. CI - Copyright (c) 2017 Elsevier Inc. All rights reserved. FAU - Chrysouli, M P AU - Chrysouli MP AD - Inorganic and Analytical Chemistry, Department of Chemistry, University of Ioannina, 45110 Ioannina, Greece. FAU - Banti, C N AU - Banti CN AD - Inorganic and Analytical Chemistry, Department of Chemistry, University of Ioannina, 45110 Ioannina, Greece. Electronic address: cbanti@cc.uoi.gr. FAU - Kourkoumelis, N AU - Kourkoumelis N AD - Medical Physics Laboratory, Medical School, University of Ioannina, Greece. FAU - Panayiotou, N AU - Panayiotou N AD - Department of Chemistry, University of Cyprus, 1678 Nicosia, Cyprus. FAU - Markopoulos, G S AU - Markopoulos GS AD - Laboratory of Biology, School of Medicine, Faculty of Health Sciences, University of Ioannina, Greece. FAU - Tasiopoulos, A J AU - Tasiopoulos AJ AD - Department of Chemistry, University of Cyprus, 1678 Nicosia, Cyprus. FAU - Hadjikakou, S K AU - Hadjikakou SK AD - Inorganic and Analytical Chemistry, Department of Chemistry, University of Ioannina, 45110 Ioannina, Greece. Electronic address: shadjika@uoi.gr. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20171108 PL - United States TA - J Inorg Biochem JT - Journal of inorganic biochemistry JID - 7905788 RN - 0 (Antineoplastic Agents) RN - 0 (Coordination Complexes) RN - 7440-57-5 (Gold) RN - 9007-49-2 (DNA) RN - 91080-16-9 (calf thymus DNA) RN - 9KJL21T0QJ (Linoleic Acid) RN - GAN16C9B8O (Glutathione) SB - IM MH - Animals MH - Antineoplastic Agents/chemistry/*pharmacology MH - Apoptosis/*drug effects MH - Cattle MH - Coordination Complexes/chemistry/*pharmacology MH - DNA/chemistry MH - DNA Damage/drug effects MH - G2 Phase Cell Cycle Checkpoints/drug effects MH - Glutathione/chemistry MH - Gold/*chemistry MH - Humans MH - Linoleic Acid/chemistry MH - Lipid Peroxidation/drug effects MH - MCF-7 Cells MH - Micronucleus Tests MH - Mitochondrial Membranes/drug effects MH - Mitotic Index MH - Molecular Docking Simulation MH - Onions/genetics MH - Permeability OTO - NOTNLM OT - Apoptosis OT - Breast cancer cells OT - Gold(I) complexes OT - Medicinal chemistry OT - Metallotherapeutic OT - Pnictogen EDAT- 2017/12/05 06:00 MHDA- 2018/06/15 06:00 CRDT- 2017/12/05 06:00 PHST- 2017/06/28 00:00 [received] PHST- 2017/10/30 00:00 [revised] PHST- 2017/11/04 00:00 [accepted] PHST- 2017/12/05 06:00 [pubmed] PHST- 2018/06/15 06:00 [medline] PHST- 2017/12/05 06:00 [entrez] AID - S0162-0134(17)30461-0 [pii] AID - 10.1016/j.jinorgbio.2017.11.004 [doi] PST - ppublish SO - J Inorg Biochem. 2018 Feb;179:107-120. doi: 10.1016/j.jinorgbio.2017.11.004. Epub 2017 Nov 8.