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Selected polyoxopalladates as promising and selective antitumor drug candidates.
Isakovic, Andjelka M; Colovic, Mirjana B; Ma, Tian; Ma, Xiang; Jeremic, Marija; Geric, Marko; Gajski, Goran; Misirlic-Dencic, Sonja; Kortz, Ulrich; Krstic, Danijela.
Afiliação
  • Isakovic AM; Institute of Medical and Clinical Biochemistry, Faculty of Medicine, University of Belgrade, Belgrade, Serbia.
  • Colovic MB; Department of Physical Chemistry, "Vinca" Institute of Nuclear Sciences-National Institute of the Republic of Serbia, University of Belgrade, Belgrade, Serbia.
  • Ma T; Department of Life Sciences and Chemistry, Jacobs University, Bremen, Germany.
  • Ma X; Department of Life Sciences and Chemistry, Jacobs University, Bremen, Germany.
  • Jeremic M; Institute of Medical and Clinical Biochemistry, Faculty of Medicine, University of Belgrade, Belgrade, Serbia.
  • Geric M; Institute for Medical Research and Occupational Health, Mutagenesis Unit, Zagreb, Croatia.
  • Gajski G; Institute for Medical Research and Occupational Health, Mutagenesis Unit, Zagreb, Croatia.
  • Misirlic-Dencic S; Institute of Medical and Clinical Biochemistry, Faculty of Medicine, University of Belgrade, Belgrade, Serbia. sonja.misirlic-dencic@med.bg.ac.rs.
  • Kortz U; Department of Life Sciences and Chemistry, Jacobs University, Bremen, Germany. u.kortz@jacobs-university.de.
  • Krstic D; Institute of Medical Chemistry, Faculty of Medicine, University of Belgrade, Belgrade, Serbia. danijela.krstic@med.bg.ac.rs.
J Biol Inorg Chem ; 26(8): 957-971, 2021 12.
Article em En | MEDLINE | ID: mdl-34549367
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.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Neuroblastoma / Antineoplásicos Limite: Humans Idioma: En Revista: J Biol Inorg Chem Ano de publicação: 2021 Tipo de documento: Article

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Neuroblastoma / Antineoplásicos Limite: Humans Idioma: En Revista: J Biol Inorg Chem Ano de publicação: 2021 Tipo de documento: Article