title: Platinum(II/IV) complexes containing ethylenediamine-N,N'-di-2/3-propionate ester ligands induced caspase-dependent apoptosis in cisplatin-resistant colon cancer cells.
abstract: Several new R(2)eddp (R = i-Pr, i-Bu; eddp = ethylenediamine-N,N'-di-3-propionate) esters and corresponding platinum(ii) and platinum(iv) complexes of the general formula [PtCl(n)(R(2)edda-type)] (n = 2, 4) were synthesized and characterized by spectroscopic methods (IR, (1)H and (13)C NMR) and elemental analysis. The crystal structure of platinum(iv) complex [PtCl(4){(c-Pe)(2)eddip}] (3a) was resolved and is given herein. Ligand precursors, platinum(ii), and platinum(iv) complexes were tested against eight tumor cell lines (CT26CL25, HTC116, SW620, PC3, LNCaP, U251, A375, and B16). Selectivity in the action of those compounds between tumor and two normal primary cells (fibroblasts and keratinocytes) are discussed. A structure-activity relationship of these compounds is discussed. Furthermore, cell cycle distribution, induction of necrosis, apoptosis, autophagy, anoikis, caspase activation, ROS, and RNS are presented on the cisplatin-resistant colon carcinoma HCT116 cell line.
authors: Institut für Chemie, Martin-Luther-Universität Halle-Wittenberg, Kurt-Mothes-Straße 2, 06120 Halle, Germany. goran.kaluderovic@chemie.uni-halle.de
authors: Goran N
authors: GN
authors: Kaluđerović
authors: Sanja A
authors: SA
authors: Mijatović
authors: Bojana B
authors: BB
authors: Zmejkovski
authors: Mirna Z
authors: MZ
authors: Bulatović
authors: Santiago
authors: S
authors: Gómez-Ruiz
authors: Marija K
authors: MK
authors: Mojić
authors: Dirk
authors: D
authors: Steinborn
authors: Djordje M
authors: DM
authors: Miljković
authors: Harry
authors: H
authors: Schmidt
authors: Stanislava D
authors: SD
authors: Stošić-Grujičić
authors: Tibor J
authors: TJ
authors: Sabo
authors: Danijela D
authors: DD
authors: Maksimović-Ivanić
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D020169:Caspases / Q000378:metabolism*; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D002945:Cisplatin / Q000737:chemistry / Q000494:pharmacology / Q000633:toxicity; D003110:Colonic Neoplasms / Q000201:enzymology* / Q000473:pathology*; D019008:Drug Resistance, Neoplasm / Q000187:drug effects*; D006801:Humans; D008024:Ligands; D051379:Mice; D008968:Molecular Conformation; D009944:Organoplatinum Compounds / Q000737:chemistry / Q000494:pharmacology* / Q000633:toxicity; D018384:Oxidative Stress / Q000187:drug effects; D026361:Reactive Nitrogen Species / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism
chemical_list: D008024:Ligands; D009944:Organoplatinum Compounds; D026361:Reactive Nitrogen Species; D017382:Reactive Oxygen Species; D020169:Caspases; D002945:Cisplatin