Open Access
Open access
International Journal of Molecular Sciences, volume 22, issue 20, pages 11065

Copper-containing nanoparticles and organic complexes: Metal reduction triggers rapid cell death via oxidative burst

Moiseeva Anna A. 2
Agadzhanian Nikol A 1
Markova Alina A. 4, 5
Tatarskiy Victor V. 6
Dukhinova Marina S 1
Ol’shevskaya Valentina A. 4
Ostroumova Olga S. 3
Shtil Alexander A. 2, 7
Publication typeJournal Article
Publication date2021-10-14
Quartile SCImago
Q1
Quartile WOS
Q1
Impact factor5.6
ISSN16616596, 14220067
Catalysis
Organic Chemistry
Inorganic Chemistry
Physical and Theoretical Chemistry
Computer Science Applications
Spectroscopy
Molecular Biology
General Medicine
Abstract

Copper-containing agents are promising antitumor pharmaceuticals due to the ability of the metal ion to react with biomolecules. In the current study, we demonstrate that inorganic Cu2+ in the form of oxide nanoparticles (NPs) or salts, as well as Cu ions in the context of organic complexes (oxidation states +1, +1.5 and +2), acquire significant cytotoxic potency (2–3 orders of magnitude determined by IC50 values) in combinations with N-acetylcysteine (NAC), cysteine, or ascorbate. In contrast, other divalent cations (Zn, Fe, Mo, and Co) evoked no cytotoxicity with these combinations. CuO NPs (0.1–1 µg/mL) together with 1 mM NAC triggered the formation of reactive oxygen species (ROS) within 2–6 h concomitantly with perturbation of the plasma membrane and caspase-independent cell death. Furthermore, NAC potently sensitized HCT116 colon carcinoma cells to Cu–organic complexes in which the metal ion coordinated with 5-(2-pyridylmethylene)-2-methylthio-imidazol-4-one or was present in the coordination sphere of the porphyrin macrocycle. The sensitization effect was detectable in a panel of mammalian tumor cell lines including the sublines with the determinants of chemotherapeutic drug resistance. The components of the combination were non-toxic if added separately. Electrochemical studies revealed that Cu cations underwent a stepwise reduction in the presence of NAC or ascorbate. This mechanism explains differential efficacy of individual Cu–organic compounds in cell sensitization depending on the availability of Cu ions for reduction. In the presence of oxygen, Cu+1 complexes can generate a superoxide anion in a Fenton-like reaction Cu+1L + O2 → O2−. + Cu+2L, where L is the organic ligand. Studies on artificial lipid membranes showed that NAC interacted with negatively charged phospholipids, an effect that can facilitate the penetration of CuO NPs across the membranes. Thus, electrochemical modification of Cu ions and subsequent ROS generation, as well as direct interaction with membranes, represent the mechanisms of irreversible membrane damage and cell death in response to metal reduction in inorganic and organic Cu-containing compounds.

Citations by journals

1
2
International Journal of Molecular Sciences
International Journal of Molecular Sciences, 2, 22.22%
International Journal of Molecular Sciences
2 publications, 22.22%
Frontiers in Endocrinology
Frontiers in Endocrinology, 1, 11.11%
Frontiers in Endocrinology
1 publication, 11.11%
Frontiers in Surgery
Frontiers in Surgery, 1, 11.11%
Frontiers in Surgery
1 publication, 11.11%
Journal of Organometallic Chemistry
Journal of Organometallic Chemistry, 1, 11.11%
Journal of Organometallic Chemistry
1 publication, 11.11%
Computational and Mathematical Methods in Medicine
Computational and Mathematical Methods in Medicine, 1, 11.11%
Computational and Mathematical Methods in Medicine
1 publication, 11.11%
Molecular Biology
Molecular Biology, 1, 11.11%
Molecular Biology
1 publication, 11.11%
Life Sciences
Life Sciences, 1, 11.11%
Life Sciences
1 publication, 11.11%
Molecules
Molecules, 1, 11.11%
Molecules
1 publication, 11.11%
1
2

Citations by publishers

1
2
3
Multidisciplinary Digital Publishing Institute (MDPI)
Multidisciplinary Digital Publishing Institute (MDPI), 3, 33.33%
Multidisciplinary Digital Publishing Institute (MDPI)
3 publications, 33.33%
Frontiers Media S.A.
Frontiers Media S.A., 2, 22.22%
Frontiers Media S.A.
2 publications, 22.22%
Elsevier
Elsevier, 2, 22.22%
Elsevier
2 publications, 22.22%
Hindawi Limited
Hindawi Limited, 1, 11.11%
Hindawi Limited
1 publication, 11.11%
Pleiades Publishing
Pleiades Publishing, 1, 11.11%
Pleiades Publishing
1 publication, 11.11%
1
2
3
  • We do not take into account publications that without a DOI.
  • Statistics recalculated only for publications connected to researchers, organizations and labs registered on the platform.
  • Statistics recalculated weekly.
Metrics
Share
Cite this
GOST |
Cite this
GOST Copy
Tsymbal S. A. et al. Copper-containing nanoparticles and organic complexes: Metal reduction triggers rapid cell death via oxidative burst // International Journal of Molecular Sciences. 2021. Vol. 22. No. 20. p. 11065.
GOST all authors (up to 50) Copy
Tsymbal S. A., Moiseeva A. A., Agadzhanian N. A., Efimova S. S., Markova A. A., Guk D. A., Krasnovskaya O. O., Alpatova V. M., Zaitsev K. V., Shibaeva A. V., Tatarskiy V. V., Dukhinova M. S., Ol’shevskaya V. A., Ostroumova O. S., Beloglazkina E. K., Shtil A. A. Copper-containing nanoparticles and organic complexes: Metal reduction triggers rapid cell death via oxidative burst // International Journal of Molecular Sciences. 2021. Vol. 22. No. 20. p. 11065.
RIS |
Cite this
RIS Copy
TY - JOUR
DO - 10.3390/ijms222011065
UR - https://doi.org/10.3390%2Fijms222011065
TI - Copper-containing nanoparticles and organic complexes: Metal reduction triggers rapid cell death via oxidative burst
T2 - International Journal of Molecular Sciences
AU - Agadzhanian, Nikol A
AU - Tatarskiy, Victor V.
AU - Dukhinova, Marina S
AU - Ol’shevskaya, Valentina A.
AU - Beloglazkina, Elena K
AU - Markova, Alina A.
AU - Shtil, Alexander A.
AU - Moiseeva, Anna A.
AU - Ostroumova, Olga S.
AU - Tsymbal, Sergey A
AU - Efimova, Svetlana S.
AU - Guk, Dmitry A.
AU - Krasnovskaya, Olga O.
AU - Alpatova, Victoria M
AU - Zaitsev, Kirill V.
AU - Shibaeva, Anna V
PY - 2021
DA - 2021/10/14 00:00:00
PB - Multidisciplinary Digital Publishing Institute (MDPI)
SP - 11065
IS - 20
VL - 22
PMID - 34681725
SN - 1661-6596
SN - 1422-0067
ER -
BibTex |
Cite this
BibTex Copy
@article{2021_Tsymbal
author = {Nikol A Agadzhanian and Victor V. Tatarskiy and Marina S Dukhinova and Valentina A. Ol’shevskaya and Elena K Beloglazkina and Alina A. Markova and Alexander A. Shtil and Anna A. Moiseeva and Olga S. Ostroumova and Sergey A Tsymbal and Svetlana S. Efimova and Dmitry A. Guk and Olga O. Krasnovskaya and Victoria M Alpatova and Kirill V. Zaitsev and Anna V Shibaeva},
title = {Copper-containing nanoparticles and organic complexes: Metal reduction triggers rapid cell death via oxidative burst},
journal = {International Journal of Molecular Sciences},
year = {2021},
volume = {22},
publisher = {Multidisciplinary Digital Publishing Institute (MDPI)},
month = {oct},
url = {https://doi.org/10.3390%2Fijms222011065},
number = {20},
pages = {11065},
doi = {10.3390/ijms222011065}
}
MLA
Cite this
MLA Copy
Tsymbal, Sergey A., et al. “Copper-containing nanoparticles and organic complexes: Metal reduction triggers rapid cell death via oxidative burst.” International Journal of Molecular Sciences, vol. 22, no. 20, Oct. 2021, p. 11065. https://doi.org/10.3390%2Fijms222011065.
Found error?