Effect of the Schiff base complex diaqua-(N-salicylidene-l-glutamato)copper(II) monohydrate on human tumor cells.

Abstract

The aim of our study was to estimate cytostatic/cytotoxic activity of the copper(II) Schiff base complex of the composition [Cu(N-salicylidene-l-glutamato)(H2O)2]·H2O, further Cu(SG-L)H2O, against human colon carcinoma cell line HT-29, as well as to determine type of cell death and to find out the molecular mechanism of apoptosis induced by this complex. Two highest concentrations (50, 100 µmol/l) of the complex showed a strong cytotoxic activity against human colon carcinoma cells HT-29 after 72 h of influence. Other concentrations had a cytostatic activity. Unchelated copper(II) ions and free ligands had no effect on the cell growth. Cu(SG-L)H2O preferentially reduced cancer cell viability compared to healthy cells (NIH-3T3). Cu(SG-L)H2O induced apoptosis of cells HT-29 at all concentrations used (1-100 µmol/l) after 48 h of influence. Apoptosis was carried out by the mitochondrial pathway with active caspases 3 and 9. By the spin-trapping technique combined with electron paramagnetic resonance we found that our complex is photochemically stable in aqueous systems and does not exhibit radical-scavenging activity when 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonate) cation radical was used as an oxidant. The complex exhibits a strong prooxidant property in the initial stages of thermal decomposition of K2S2O8 in water solutions leading to the massive production of (·)OH radicals. Therefore, this complex could strongly participate in anticancer action via a free radical mechanism.

• Authors: Katarina Konarikova, Lucia Andrezalova, Peter Rapta, Marianna Slovakova, Zdenka Durackova, Lucia Laubertova, Helena Gbelcova, Lubomir Danisovic, Daniel Bohmer, Tomas Ruml, Martin Sveda, Ingrid Zitnanova
• Journal: European journal of pharmacology (Eur J Pharmacol) Vol. 721 Issue 1-3 Pg. 178-84 (Dec 05 2013) ISSN: 1879-0712 [Electronic] Netherlands
• PMID: 24113525 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2013 Elsevier B.V. All rights reserved.

Chemical References

• (N-salicylidene-L-glutamato)copper(II) monohydrate
• Antineoplastic Agents
• Antioxidants
• Organometallic Compounds
• Schiff Bases
• Caspases

Topics

• Antineoplastic Agents (chemistry, pharmacology)
• Antioxidants (chemistry, pharmacology)
• Caspases (metabolism)
• Cell Death (drug effects)
• Cell Proliferation (drug effects)
• HT29 Cells
• Humans
• Hydrogen Bonding
• Organometallic Compounds (chemistry, pharmacology)
• Schiff Bases (chemistry)
• Structure-Activity Relationship