TY  - CONF
AU  - Čolović, Mirjana B.
AU  - Ma, Tian
AU  - Ma, Xiang
AU  - Isaković, Anđelka
AU  - Misirlić-Denčić, Sonja
AU  - Kortz, Urlich
AU  - Krstić, Danijela
PY  - 2021
UR  - https://vinar.vin.bg.ac.rs/handle/123456789/13018
AB  - Polyoxopalladates (POPs) are discrete, anionic palladium(II)- oxo nanoclusters combining properties of polyoxometalates and palladium(II), and thus are highly promising for the development of novel antitumor metallodrugs. The aim of this study was to investigate in vitro the influence of three POP salts with approved anti-neuroblastoma action, Na8[Pd13As8O34(OH)6]·42H2O (Pd13), Na4[SrPd12O6(OH)3(PhAsO3)6(OAc)3]·2NaOAc·32H2O (SrPd12), and Na6[Pd13O8(PhAsO3)8]·23H2O (Pd13L), on E-NTPDase activity using rat synaptic plasma membranes (SPMs) isolated from Wistar brain as a model system. Dose-dependent inhibition of ENTPDases was obtained within concentration range 2 × 10-6 - 1 × 10-3 mol/L for all investigated POPs. Inhibition parameters, IC50 value and Hill's coefficient, nH, were determined by sigmoidal fitting the experimental results. The calculated IC50 values were (1.08 ± 0.25) × 10-4 , (1.19 ± 0.13) × 10-4 , and (2.06 ± 0.88) × 10-4 mol/L for Pd13, SrPd12, and Pd13L, respectively, indicating their similar inhibitory strengths. The nH values were determined to be < 1, indicating negatively cooperative binding for all POPs studied. The observed inhibitory effect of these anti-neuroblastoma POPs on ENTPDase activity suggest that the inhibition of E-NTPDases, the enzymes representing the major part of purinergic signaling, could be considered as a putative mechanism of antitumor action and a new strategy in the development of novel antitumor therapeutics.
PB  - Belgrade : Society of Physical Chemists of Serbia
C3  - PHYSICAL CHEMISTRY 2021 : 15th international conference on fundamental and applied aspects of physical chemistry : Book of abstracts
T1  - Influence of polyoxopalladates(II) on ecto-nucleoside triphosphate diphosphohydrolases
SP  - 77
EP  - 77
UR  - https://hdl.handle.net/21.15107/rcub_vinar_13018
ER  - 

@conference{
author = "Čolović, Mirjana B. and Ma, Tian and Ma, Xiang and Isaković, Anđelka and Misirlić-Denčić, Sonja and Kortz, Urlich and Krstić, Danijela",
year = "2021",
abstract = "Polyoxopalladates (POPs) are discrete, anionic palladium(II)- oxo nanoclusters combining properties of polyoxometalates and palladium(II), and thus are highly promising for the development of novel antitumor metallodrugs. The aim of this study was to investigate in vitro the influence of three POP salts with approved anti-neuroblastoma action, Na8[Pd13As8O34(OH)6]·42H2O (Pd13), Na4[SrPd12O6(OH)3(PhAsO3)6(OAc)3]·2NaOAc·32H2O (SrPd12), and Na6[Pd13O8(PhAsO3)8]·23H2O (Pd13L), on E-NTPDase activity using rat synaptic plasma membranes (SPMs) isolated from Wistar brain as a model system. Dose-dependent inhibition of ENTPDases was obtained within concentration range 2 × 10-6 - 1 × 10-3 mol/L for all investigated POPs. Inhibition parameters, IC50 value and Hill's coefficient, nH, were determined by sigmoidal fitting the experimental results. The calculated IC50 values were (1.08 ± 0.25) × 10-4 , (1.19 ± 0.13) × 10-4 , and (2.06 ± 0.88) × 10-4 mol/L for Pd13, SrPd12, and Pd13L, respectively, indicating their similar inhibitory strengths. The nH values were determined to be < 1, indicating negatively cooperative binding for all POPs studied. The observed inhibitory effect of these anti-neuroblastoma POPs on ENTPDase activity suggest that the inhibition of E-NTPDases, the enzymes representing the major part of purinergic signaling, could be considered as a putative mechanism of antitumor action and a new strategy in the development of novel antitumor therapeutics.",
publisher = "Belgrade : Society of Physical Chemists of Serbia",
journal = "PHYSICAL CHEMISTRY 2021 : 15th international conference on fundamental and applied aspects of physical chemistry : Book of abstracts",
title = "Influence of polyoxopalladates(II) on ecto-nucleoside triphosphate diphosphohydrolases",
pages = "77-77",
url = "https://hdl.handle.net/21.15107/rcub_vinar_13018"
}

Čolović, M. B., Ma, T., Ma, X., Isaković, A., Misirlić-Denčić, S., Kortz, U.,& Krstić, D.. (2021). Influence of polyoxopalladates(II) on ecto-nucleoside triphosphate diphosphohydrolases. in PHYSICAL CHEMISTRY 2021 : 15th international conference on fundamental and applied aspects of physical chemistry : Book of abstracts
Belgrade : Society of Physical Chemists of Serbia., 77-77.
https://hdl.handle.net/21.15107/rcub_vinar_13018

Čolović MB, Ma T, Ma X, Isaković A, Misirlić-Denčić S, Kortz U, Krstić D. Influence of polyoxopalladates(II) on ecto-nucleoside triphosphate diphosphohydrolases. in PHYSICAL CHEMISTRY 2021 : 15th international conference on fundamental and applied aspects of physical chemistry : Book of abstracts. 2021;:77-77.
https://hdl.handle.net/21.15107/rcub_vinar_13018 .

Čolović, Mirjana B., Ma, Tian, Ma, Xiang, Isaković, Anđelka, Misirlić-Denčić, Sonja, Kortz, Urlich, Krstić, Danijela, "Influence of polyoxopalladates(II) on ecto-nucleoside triphosphate diphosphohydrolases" in PHYSICAL CHEMISTRY 2021 : 15th international conference on fundamental and applied aspects of physical chemistry : Book of abstracts (2021):77-77,
https://hdl.handle.net/21.15107/rcub_vinar_13018 .

TY  - JOUR
AU  - Isaković, Anđelka
AU  - Čolović, Mirjana B.
AU  - Ma, Tian
AU  - Ma, Xiang
AU  - Jeremić, Marija
AU  - Gerić, Marko
AU  - Gajski, Goran
AU  - Misirlić-Denčić, Sonja
AU  - Kortz, Ulrich
AU  - Krstić, Danijela Z.
PY  - 2021
UR  - https://vinar.vin.bg.ac.rs/handle/123456789/9952
AB  - Polyoxo-noble-metalates (PONMs), a class of molecular noble metal-oxo nanoclusters that combine features of both polyoxometalates and noble metals, are a promising platform for the development of next-generation antitumor metallodrugs. This study aimed to evaluate the antitumor potential against human neuroblastoma cells (SH-SY5Y), as well as toxicity towards healthy human peripheral blood cells (HPBCs), of five polyoxopalladates(II): (Na8[Pd13As8O34(OH)6]·42H2O (Pd13), Na4[SrPd12O6(OH)3(PhAsO3)6(OAc)3]·2NaOAc·32H2O (SrPd12), Na6[Pd13(AsPh)8O32]·23H2O (Pd13L), Na12[SnO8Pd12(PO4)8]·43H2O (SnPd12), and Na12[PbO8Pd12(PO4)8]·38H2O (PbPd12)), as the largest subset of PONMs. A pure inorganic, Pd13, was found as the most potent and selective antineuroblastoma agent with IC50 values (µM) of 7.2 ± 2.2 and 4.4 ± 1.2 for 24 and 48 h treatment, respectively, even lower than cisplatin (28.4 ± 7.4 and 11.6 ± 0.8). The obtained IC50 values (µM) for 24/48 h treatment with SrPd12 and Pd13L were 75.8 ± 6.7/76.7 ± 22.9 and 63.8 ± 3.6/21.4 ± 10.8, respectively, whereas SnPd12 and PbPd12 did not remarkably affect the SH-SY5Y viability (IC50 > > 100 µM). Pd13 caused depolarisation of inner mitochondrial membrane prior to superoxide ion hyperproduction, followed by caspase activation, DNA fragmentation and cell cycle arrest, all hallmarks of apoptotic cell death, and accompanied by an increase in acidic vesicles content, suggestive of autophagy induction. Importantly, Pd13 demonstrated the antitumor effect at concentrations not cytogenotoxic for normal HPBCs. On the contrary, SrPd12 and Pd13L at concentrations ≥ 1/3 IC50 (24 h) decreased HPBC viability and increased % tail DNA up to 42% and 3.05 times, respectively, related to control. SnPd12 and PbPd12, previously confirmed promising antileukemic agents, did not exhibit cytogenotoxicity to HPBCs, and thus could be regarded as tumor cell specific and selective drug candidates.
T2  - JBIC Journal of Biological Inorganic Chemistry
T1  - Selected polyoxopalladates as promising and selective antitumor drug candidates
VL  - 26
IS  - 8
SP  - 957
EP  - 971
DO  - 10.1007/s00775-021-01905-4
ER  - 

@article{
author = "Isaković, Anđelka and Čolović, Mirjana B. and Ma, Tian and Ma, Xiang and Jeremić, Marija and Gerić, Marko and Gajski, Goran and Misirlić-Denčić, Sonja and Kortz, Ulrich and Krstić, Danijela Z.",
year = "2021",
abstract = "Polyoxo-noble-metalates (PONMs), a class of molecular noble metal-oxo nanoclusters that combine features of both polyoxometalates and noble metals, are a promising platform for the development of next-generation antitumor metallodrugs. This study aimed to evaluate the antitumor potential against human neuroblastoma cells (SH-SY5Y), as well as toxicity towards healthy human peripheral blood cells (HPBCs), of five polyoxopalladates(II): (Na8[Pd13As8O34(OH)6]·42H2O (Pd13), Na4[SrPd12O6(OH)3(PhAsO3)6(OAc)3]·2NaOAc·32H2O (SrPd12), Na6[Pd13(AsPh)8O32]·23H2O (Pd13L), Na12[SnO8Pd12(PO4)8]·43H2O (SnPd12), and Na12[PbO8Pd12(PO4)8]·38H2O (PbPd12)), as the largest subset of PONMs. A pure inorganic, Pd13, was found as the most potent and selective antineuroblastoma agent with IC50 values (µM) of 7.2 ± 2.2 and 4.4 ± 1.2 for 24 and 48 h treatment, respectively, even lower than cisplatin (28.4 ± 7.4 and 11.6 ± 0.8). The obtained IC50 values (µM) for 24/48 h treatment with SrPd12 and Pd13L were 75.8 ± 6.7/76.7 ± 22.9 and 63.8 ± 3.6/21.4 ± 10.8, respectively, whereas SnPd12 and PbPd12 did not remarkably affect the SH-SY5Y viability (IC50 > > 100 µM). Pd13 caused depolarisation of inner mitochondrial membrane prior to superoxide ion hyperproduction, followed by caspase activation, DNA fragmentation and cell cycle arrest, all hallmarks of apoptotic cell death, and accompanied by an increase in acidic vesicles content, suggestive of autophagy induction. Importantly, Pd13 demonstrated the antitumor effect at concentrations not cytogenotoxic for normal HPBCs. On the contrary, SrPd12 and Pd13L at concentrations ≥ 1/3 IC50 (24 h) decreased HPBC viability and increased % tail DNA up to 42% and 3.05 times, respectively, related to control. SnPd12 and PbPd12, previously confirmed promising antileukemic agents, did not exhibit cytogenotoxicity to HPBCs, and thus could be regarded as tumor cell specific and selective drug candidates.",
journal = "JBIC Journal of Biological Inorganic Chemistry",
title = "Selected polyoxopalladates as promising and selective antitumor drug candidates",
volume = "26",
number = "8",
pages = "957-971",
doi = "10.1007/s00775-021-01905-4"
}

Isaković, A., Čolović, M. B., Ma, T., Ma, X., Jeremić, M., Gerić, M., Gajski, G., Misirlić-Denčić, S., Kortz, U.,& Krstić, D. Z.. (2021). Selected polyoxopalladates as promising and selective antitumor drug candidates. in JBIC Journal of Biological Inorganic Chemistry, 26(8), 957-971.
https://doi.org/10.1007/s00775-021-01905-4

Isaković A, Čolović MB, Ma T, Ma X, Jeremić M, Gerić M, Gajski G, Misirlić-Denčić S, Kortz U, Krstić DZ. Selected polyoxopalladates as promising and selective antitumor drug candidates. in JBIC Journal of Biological Inorganic Chemistry. 2021;26(8):957-971.
doi:10.1007/s00775-021-01905-4 .

Isaković, Anđelka, Čolović, Mirjana B., Ma, Tian, Ma, Xiang, Jeremić, Marija, Gerić, Marko, Gajski, Goran, Misirlić-Denčić, Sonja, Kortz, Ulrich, Krstić, Danijela Z., "Selected polyoxopalladates as promising and selective antitumor drug candidates" in JBIC Journal of Biological Inorganic Chemistry, 26, no. 8 (2021):957-971,
https://doi.org/10.1007/s00775-021-01905-4 . .