Abstract
Background: Copper has shown to be useful in disorders with an inflammation origin such as cancer [1-3]. It has previously shown that Casiopeínas® interact with DNA and promote the disruption by a mechanism related to the increase in the level of free radicals [4-6] which confers antineoplastic potential.
Objetive: The aim of the present work was to study the antitumor effects of a series of Cu(II) complexes with saccharinate (sac) and glutamate (gln): [Cu(sac)2(H2O)4].2H2O (Cu-sac), [Cu(gln)2] (Cu-gln) and Na2[Cu(sac)2 (gln)2].H2O (Cu-sac-gln). Methods: We have investigated the action of these compounds on cell viability on human osteosarcoma cells MG-63. In particular, we pay special attention to the cyto and genotoxicity actions of these complexes and to the association to oxidative stress. Results: The three complexes: Cu-sac, Cu-gln and Cu-sac-gln caused a decline in cell viability. The half-maximal inhibitory concentration in MG-63 cells for Cu-sac-gln is 170 µM, showing the strongest antiproliferative effect. Moreover, only Cu-sac-gln caused a decrease of the mitochondrial activity from 100 µM. Our results indicate that the copper(II) complexes studied here produce DNA damage and suggest that the rise of reactive oxygen species (ROS) is the central mechanism action. Genotoxicity studied by the Cytokinesis-block micronucleus (MN) assay and the Single cell gel electrophoresis (comet assay) could be observed in MG-63 cells treated with Cu-sac-gln from 100 and 50 µM, respectively. Cu-sac and Cu-gln also induced DNA damage; however their effect was definitively weaker. The generation of reactive oxygen species increased from 50 μM of Cu-sac-gln and Cu-sac and only from 250 µM of Cugln, as well as a reduction of the GSH/GSSG ratio from 50 µM. When cells were treated with several concentrations of the complexes in addition to a combination of 50 μM of vitamin C plus 50 µM of vitamin E, a total recovery in cell survival was obtained for Cu-gln in the whole range of tested concentrations while only a partial viability recovery was obtained from 250 µM of Cu-sac and Cu-sac-gln. Conclusion: Overall, our results point to a differential cyto- and genotoxicity of the three copper(II) complexes and demonstrate that the complexation with both ligands confers the most potent antitumor action in human osteosarcoma cells.Keywords: Copper(II) complexes, antitumor drugs, cytotoxicity, genotoxicity, human osteosarcoma cells.
Graphical Abstract
Call for Papers in Thematic Issues
Induction of cell death in cancer cells by modulating telomerase activity using small molecule drugs
Telomeres are distinctive but short stretches present at the corners of chromosomes and aid in stabilizing chromosomal makeup. Resynthesis of telomeres supported by the activity of reverse transcriptase ribonucleoprotein complex telomerase. There is no any telomerase activity in human somatic cells, but the stem cells and germ cells undergone telomerase ...read more
Role of natural compounds as anti anti-cancer agents
Cancer is considered the leading cause of worldwide mortality, accounting for nearly 10 million deaths in 2022. Cancer outcome can be improved through an appropriate screening and early detection and through an efficient clinical treatment. Chemotherapy remains an important approach in treatment o f several types of cancers, even though ...read more
Signaling and enzymatic modulators in cancer treatment
Cancer accounts for nearly 10 million deaths in 2022 and is considered the leading cause of worldwide mortality. Cancer outcome can be improved through an appropriate screening and early detection and through an efficient clinical treatment. Chemotherapy, radiotherapy and surgery are the most important approach for the treatment of several ...read more
Related Journals
Anti-Inflammatory & Anti-Allergy Agents in Medicinal Chemistry
Current Analytical Chemistry
Current Computer-Aided Drug Design
Current Bioactive Compounds
Current Cancer Drug Targets
Combinatorial Chemistry & High Throughput Screening
Current Cancer Therapy Reviews
Current Diabetes Reviews
Current Drug Safety
Current Drug Targets
Related Books
Drug Addiction Mechanisms in the Brain
Botanicals and Natural Bioactives: Prevention and Treatment of Diseases
Software and Programming Tools in Pharmaceutical Research
Objective Pharmaceutics: A Comprehensive Compilation of Questions and Answers for Pharmaceutics Exam Prep
Biosurfactants: A Boon to Healthcare, Agriculture & Environmental Sustainability
Medicinal Chemistry of Drugs Affecting Cardiovascular and Endocrine Systems
Frontiers in Computational Chemistry
Frontiers in Clinical Drug Research - Anti-Cancer Agents
The Management of Metastatic Triple-Negative Breast Cancer: An Integrated and Expeditionary Approach
Advances in Dye Degradation
47
3