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Drug combination study of novel oxorhenium(V) complexes

Authorized Users Only
2022
Authors
Petrović, Tamara
Gligorijević, Nevenka
Belaj, Ferdinand
Aranđelović, Sandra
Mihajlović-Lalić, Ljiljana E.
Grgurić-Šipka, Sanja
Poljarević, Jelena
Article (Published version)
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Abstract
Three Re(V) complexes of structural formulas [ReOCl2L(PPh3)], where L is pyridine-2-carboxylic acid (C1), 3- methyl-pyridine-2-carboxylic acid (C2) and 6-methyl-pyridine-2-carboxylic acid (C3) were synthesized and characterized using NMR, IR spectroscopy and mass spectrometry. Crystal structures of all three complexes have been additionally confirmed by X-ray analysis. The biological activity has been investigated in the panel of tumor cell lines A549, PANC-1, MDA-MB-231, MCF-7, LS-174, EAhy.926 and one in non-tumor cell line MRC-5. Only C1 showed dose-dependent cytotoxic potential, particularly toward triple-negative breast adenocarcinoma cells MDA-MB-231 with IC50 68.90 ± 1.73 μM and pancreatic adenocarcinoma cells PANC-1 with IC50 69.84 ± 2.3 μM. Both cell lines are characterized by a highly invasive and resistant phenotype. Drug combination studies in PANC-1 cells with C1 and Verapamil hydrochloride (VRP), which is the established inhibitor of efflux transporter P-glycopro...tein (Pgp), revealed enhancement of antiproliferative action of the complex in a dose-dependent manner, and slight arrest of cell cycle in the S phase. Also, a depletion of the glutathione (GSH) level by Lbuthionine-sulfoximine (L-BSO) at sub-toxic concentrations (100 μM) caused an increase of activity of C1 to the IC50 57.67 ± 6.51 (μM). A morphological analysis in PANC-1 cells by dual acridine orange/ethidium bromide staining, revealed apoptotic potential of complex C1 and a slower kinetic of cell death induction, suggesting a different mechanism of action compared to cisplatin.

Keywords:
Rhenium(V) complex Crystal structure / Cytotoxic activity / Breast carcinoma cells / Pancreatic carcinoma cells / Gluthation pathway
Source:
Journal of Inorganic Biochemistry, 2022, 231, 111807-
Publisher:
  • Elsevier
Funding / projects:
  • Ministry of Education, Science and Technological Development, Republic of Serbia, Grant no. 200168 (University of Belgrade, Faculty of Chemistry) (RS-200168)
  • Ministry of Education, Science and Technological Development, Republic of Serbia, Grant no. 200043 (Institute of Oncology and Radiology of Serbia, Belgrade) (RS-200043)
  • Ministry of Education, Science and Technological Development, Republic of Serbia, Grant no. 200288 (Innovation Center of the Faculty of Chemistry) (RS-200288)
Note:
  • Peer-reviewed manuscript: https://cherry.chem.bg.ac.rs/handle/123456789/5047

DOI: 10.1016/j.jinorgbio.2022.111807

ISSN: 0162-0134

WoS: 00079039560000

Scopus: 2-s2.0-85127128084
[ Google Scholar ]
URI
http://cherry.chem.bg.ac.rs/handle/123456789/5046
Collections
  • Publikacije
Institution/Community
Hemijski fakultet
TY  - JOUR
AU  - Petrović, Tamara
AU  - Gligorijević, Nevenka
AU  - Belaj, Ferdinand
AU  - Aranđelović, Sandra
AU  - Mihajlović-Lalić, Ljiljana E.
AU  - Grgurić-Šipka, Sanja
AU  - Poljarević, Jelena
PY  - 2022
UR  - http://cherry.chem.bg.ac.rs/handle/123456789/5046
AB  - Three Re(V) complexes of structural formulas [ReOCl2L(PPh3)], where L is pyridine-2-carboxylic acid (C1), 3-
methyl-pyridine-2-carboxylic acid (C2) and 6-methyl-pyridine-2-carboxylic acid (C3) were synthesized and
characterized using NMR, IR spectroscopy and mass spectrometry. Crystal structures of all three complexes have
been additionally confirmed by X-ray analysis. The biological activity has been investigated in the panel of tumor
cell lines A549, PANC-1, MDA-MB-231, MCF-7, LS-174, EAhy.926 and one in non-tumor cell line MRC-5. Only
C1 showed dose-dependent cytotoxic potential, particularly toward triple-negative breast adenocarcinoma cells
MDA-MB-231 with IC50 68.90 ± 1.73 μM and pancreatic adenocarcinoma cells PANC-1 with IC50 69.84 ± 2.3
μM. Both cell lines are characterized by a highly invasive and resistant phenotype. Drug combination studies in
PANC-1 cells with C1 and Verapamil hydrochloride (VRP), which is the established inhibitor of efflux transporter
P-glycoprotein (Pgp), revealed enhancement of antiproliferative action of the complex in a dose-dependent
manner, and slight arrest of cell cycle in the S phase. Also, a depletion of the glutathione (GSH) level by Lbuthionine-sulfoximine (L-BSO) at sub-toxic concentrations (100 μM) caused an increase of activity of C1 to the
IC50 57.67 ± 6.51 (μM). A morphological analysis in PANC-1 cells by dual acridine orange/ethidium bromide
staining, revealed apoptotic potential of complex C1 and a slower kinetic of cell death induction, suggesting a
different mechanism of action compared to cisplatin.
PB  - Elsevier
T2  - Journal of Inorganic Biochemistry
T1  - Drug combination study of novel oxorhenium(V) complexes
VL  - 231
SP  - 111807
DO  - 10.1016/j.jinorgbio.2022.111807
ER  - 
@article{
author = "Petrović, Tamara and Gligorijević, Nevenka and Belaj, Ferdinand and Aranđelović, Sandra and Mihajlović-Lalić, Ljiljana E. and Grgurić-Šipka, Sanja and Poljarević, Jelena",
year = "2022",
abstract = "Three Re(V) complexes of structural formulas [ReOCl2L(PPh3)], where L is pyridine-2-carboxylic acid (C1), 3-
methyl-pyridine-2-carboxylic acid (C2) and 6-methyl-pyridine-2-carboxylic acid (C3) were synthesized and
characterized using NMR, IR spectroscopy and mass spectrometry. Crystal structures of all three complexes have
been additionally confirmed by X-ray analysis. The biological activity has been investigated in the panel of tumor
cell lines A549, PANC-1, MDA-MB-231, MCF-7, LS-174, EAhy.926 and one in non-tumor cell line MRC-5. Only
C1 showed dose-dependent cytotoxic potential, particularly toward triple-negative breast adenocarcinoma cells
MDA-MB-231 with IC50 68.90 ± 1.73 μM and pancreatic adenocarcinoma cells PANC-1 with IC50 69.84 ± 2.3
μM. Both cell lines are characterized by a highly invasive and resistant phenotype. Drug combination studies in
PANC-1 cells with C1 and Verapamil hydrochloride (VRP), which is the established inhibitor of efflux transporter
P-glycoprotein (Pgp), revealed enhancement of antiproliferative action of the complex in a dose-dependent
manner, and slight arrest of cell cycle in the S phase. Also, a depletion of the glutathione (GSH) level by Lbuthionine-sulfoximine (L-BSO) at sub-toxic concentrations (100 μM) caused an increase of activity of C1 to the
IC50 57.67 ± 6.51 (μM). A morphological analysis in PANC-1 cells by dual acridine orange/ethidium bromide
staining, revealed apoptotic potential of complex C1 and a slower kinetic of cell death induction, suggesting a
different mechanism of action compared to cisplatin.",
publisher = "Elsevier",
journal = "Journal of Inorganic Biochemistry",
title = "Drug combination study of novel oxorhenium(V) complexes",
volume = "231",
pages = "111807",
doi = "10.1016/j.jinorgbio.2022.111807"
}
Petrović, T., Gligorijević, N., Belaj, F., Aranđelović, S., Mihajlović-Lalić, L. E., Grgurić-Šipka, S.,& Poljarević, J.. (2022). Drug combination study of novel oxorhenium(V) complexes. in Journal of Inorganic Biochemistry
Elsevier., 231, 111807.
https://doi.org/10.1016/j.jinorgbio.2022.111807
Petrović T, Gligorijević N, Belaj F, Aranđelović S, Mihajlović-Lalić LE, Grgurić-Šipka S, Poljarević J. Drug combination study of novel oxorhenium(V) complexes. in Journal of Inorganic Biochemistry. 2022;231:111807.
doi:10.1016/j.jinorgbio.2022.111807 .
Petrović, Tamara, Gligorijević, Nevenka, Belaj, Ferdinand, Aranđelović, Sandra, Mihajlović-Lalić, Ljiljana E., Grgurić-Šipka, Sanja, Poljarević, Jelena, "Drug combination study of novel oxorhenium(V) complexes" in Journal of Inorganic Biochemistry, 231 (2022):111807,
https://doi.org/10.1016/j.jinorgbio.2022.111807 . .

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