Selected polyoxopalladates as promising and selective antitumor drug candidates
Samo za registrovane korisnike
2021
Autori
Isaković, AnđelkaČolović, Mirjana B.
Ma, Tian
Ma, Xiang
Jeremić, Marija
Gerić, Marko
Gajski, Goran
Misirlić-Denčić, Sonja
Kortz, Ulrich
Krstić, Danijela Z.
Članak u časopisu (Objavljena verzija)
Metapodaci
Prikaz svih podataka o dokumentuApstrakt
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.
Izvor:
JBIC Journal of Biological Inorganic Chemistry, 2021, 26, 8, 957-971Finansiranje / projekti:
- Ministarstvo nauke, tehnološkog razvoja i inovacija Republike Srbije, institucionalno finansiranje - 200110 (Univerzitet u Beogradu, Medicinski fakultet) (RS-MESTD-inst-2020-200110)
- Ministarstvo nauke, tehnološkog razvoja i inovacija Republike Srbije, institucionalno finansiranje - 200017 (Univerzitet u Beogradu, Institut za nuklearne nauke Vinča, Beograd-Vinča) (RS-MESTD-inst-2020-200017)
- German Research Council [DFG, KO-2288/20-1]
- Serbia-Germany bilateral project [451-03- 01038/2015-09/16, DAAD-PPP]
- Serbia-Croatia bilateral project [337-00-205/2019-09/19]
- COST Actions: CMST [CA16113, CA15132, CA16113, STSM 44119, 44120]
DOI: 10.1007/s00775-021-01905-4
ISSN: 1432-1327
PubMed: 34549367
WoS: 000698191700001
Scopus: 2-s2.0-85115254523
Kolekcije
Institucija/grupa
VinčaTY - 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 . .