Publication Type Journal Article
Title Evaluation of cellular uptake, cytotoxicity and cellular ultrastructural effects of heteroleptic oxidovanadium(IV) complexes of salicylaldimines and polypyridyl ligands
Authors Gonzalo Scalese Isabel Correia Julio Benitez Santiago Rostan Fernanda M. Marques Filipa Mendes Antonio Pedro Matos J.C. Pessoa Dinorah Gambino
Groups BIOIN
Journal JOURNAL OF INORGANIC BIOCHEMISTRY
Year 2017
Month January
Volume 166
Number
Pages 162-172
Abstract Searching for prospective vanadium-based drugs for cancer treatment, a new series of structurally related [(VO)-O-IV(L-2H)(NN)] compounds (1-8) was developed. They include a double deprotonated salicylaldimine Schiff base ligand (L-2H) and different NN-polypyridyl co-ligands having DNA intercalating capacity. Compounds were characterized in solid state and in solution. EPR spectroscopy suggests that the NN ligands act as bidentate and bind through both nitrogen donor atoms in an axial-equatorial mode. The cytotoxicity was evaluated in human tumoral cells (ovarian A2780, breast MCF7, prostate PO). The cytotoxic activity was dependent on type of cell and incubation time. At 24 h PC3 cells presented low sensitivity, but at 72 h all complexes showed high cytotoxic activity in all cells. Human kidney HEK293 and ovarian cisplatin resistant A2780cisR cells were also included to evaluate selectivity towards cancer cells and potency to overcome cisplatin resistance, respectively. Most complexes showed no detectable interaction with plasmid DNA, except 2 and 7 which depicted low ability to induce single strand breaks in supercoiled DNA. Based on the overall cytotoxic profile, complexes with 2,2 -bipyridine and 1,10-phenanthroline ligands (1 and 2) were selected for further studies, which consisted on cellular distribution and ultrastructural analyses. In the A2780 cells both depicted different distribution profiles; the former accumulates mostly at the membrane and the latter in the cytoskeleton. Morphology of treated cells showed nuclear atypia and membrane alterations, more severe for 1. Complexes induce different cell death pathways, predominantly necrosis for 1 and apoptosis for 2. Complexes alternative mode of cell death motivates the possibility for further developments. (C) 2016 Elsevier Inc. All rights reserved.
DOI http://dx.doi.org/10.1016/j.jinorgbio.2016.11.010
ISBN
Publisher ELSEVIER SCIENCE INC
Book Title
ISSN 0162-0134
EISSN 1873-3344
Conference Name
Bibtex ID ISI:000390978100020
Observations
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