Improved in vitro antitumor potential of (O,O'-Diisobutyl-ethylenediamine-N,N'-di-3-propionate)tetrachloridoplatinum(IV) complex under normoxic and hypoxic conditions
Authorized Users Only
2015
Authors
Bulatović, MirnaKaluderovic, Milena R
Mojic, Marija
Zmejkovski, Bojana
Hey-Hawkins, Evamarie
Vidakovic, Melita
Grdovic, Nevena
Kaluđerović, Goran N.
Mijatović, Sanja
Maksimović-Ivanić, Danijela D.
Article (Published version)
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Show full item recordAbstract
(O,O'-Diisobutyl-ethylenediamine-N,N'-di-3-propionate)tetrachloridoplatinum(IV), [PtCl4(iBu(2)eddp)]. shows an improved pharmacological profile in comparison to cisplatin. This is manifested through accelerated dying process led by necrotic cell death, reflected through mitochondrial collapse, strong ATP depletion and reactive oxygen species production. Loss of mitochondrial potential was further followed with intensive apoptosis that finalized with DNA fragmentation. Different dynamic of tumoricidal action could be partly ascribed to less affected repair mechanisms in comparison to cisplatin. Importantly, [PtCl4(iBu(2)eddp)] did not induce necrosis in primary fibroblasts suggesting different intracellular response of normal vs. tumor cells. This selectivity toward malignant phenotype is further confirmed by retained tumoricidal potential in hypoxic conditions, while cisplatin became completely inefficient.
Keywords:
Platinum(IV) complex / Cisplatin / ATP depletion / Mitochondrial collapse / Oxidative stress / Hypoxic conditionsSource:
European Journal of Pharmacology, 2015, 760, 136-144Publisher:
- Elsevier
Funding / projects:
- Molecular mechanisms of physiological and pharmacological control of inflammation and cancer (RS-MESTD-Basic Research (BR or ON)-173013)
- Signaling molecules in diabetes: search for potential targets in intrinsic pathways for prediction and intervention in diabetes (RS-MESTD-Basic Research (BR or ON)-173020)
- Rational design and synthesis of biologically active and coordination compounds and functional materials, relevant for (bio)nanotechnology (RS-MESTD-Basic Research (BR or ON)-172035)
- SMWK - 33707045
- SAB (ESF) - 100147954
- Free State of Saxony - 100099597
DOI: 10.1016/j.ejphar.2015.04.012
ISSN: 0014-2999
PubMed: 25912798
WoS: 000355664200017
Scopus: 2-s2.0-84929457797
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Institution/Community
IHTMTY - JOUR AU - Bulatović, Mirna AU - Kaluderovic, Milena R AU - Mojic, Marija AU - Zmejkovski, Bojana AU - Hey-Hawkins, Evamarie AU - Vidakovic, Melita AU - Grdovic, Nevena AU - Kaluđerović, Goran N. AU - Mijatović, Sanja AU - Maksimović-Ivanić, Danijela D. PY - 2015 UR - https://cer.ihtm.bg.ac.rs/handle/123456789/1650 AB - (O,O'-Diisobutyl-ethylenediamine-N,N'-di-3-propionate)tetrachloridoplatinum(IV), [PtCl4(iBu(2)eddp)]. shows an improved pharmacological profile in comparison to cisplatin. This is manifested through accelerated dying process led by necrotic cell death, reflected through mitochondrial collapse, strong ATP depletion and reactive oxygen species production. Loss of mitochondrial potential was further followed with intensive apoptosis that finalized with DNA fragmentation. Different dynamic of tumoricidal action could be partly ascribed to less affected repair mechanisms in comparison to cisplatin. Importantly, [PtCl4(iBu(2)eddp)] did not induce necrosis in primary fibroblasts suggesting different intracellular response of normal vs. tumor cells. This selectivity toward malignant phenotype is further confirmed by retained tumoricidal potential in hypoxic conditions, while cisplatin became completely inefficient. PB - Elsevier T2 - European Journal of Pharmacology T1 - Improved in vitro antitumor potential of (O,O'-Diisobutyl-ethylenediamine-N,N'-di-3-propionate)tetrachloridoplatinum(IV) complex under normoxic and hypoxic conditions VL - 760 SP - 136 EP - 144 DO - 10.1016/j.ejphar.2015.04.012 ER -
@article{ author = "Bulatović, Mirna and Kaluderovic, Milena R and Mojic, Marija and Zmejkovski, Bojana and Hey-Hawkins, Evamarie and Vidakovic, Melita and Grdovic, Nevena and Kaluđerović, Goran N. and Mijatović, Sanja and Maksimović-Ivanić, Danijela D.", year = "2015", abstract = "(O,O'-Diisobutyl-ethylenediamine-N,N'-di-3-propionate)tetrachloridoplatinum(IV), [PtCl4(iBu(2)eddp)]. shows an improved pharmacological profile in comparison to cisplatin. This is manifested through accelerated dying process led by necrotic cell death, reflected through mitochondrial collapse, strong ATP depletion and reactive oxygen species production. Loss of mitochondrial potential was further followed with intensive apoptosis that finalized with DNA fragmentation. Different dynamic of tumoricidal action could be partly ascribed to less affected repair mechanisms in comparison to cisplatin. Importantly, [PtCl4(iBu(2)eddp)] did not induce necrosis in primary fibroblasts suggesting different intracellular response of normal vs. tumor cells. This selectivity toward malignant phenotype is further confirmed by retained tumoricidal potential in hypoxic conditions, while cisplatin became completely inefficient.", publisher = "Elsevier", journal = "European Journal of Pharmacology", title = "Improved in vitro antitumor potential of (O,O'-Diisobutyl-ethylenediamine-N,N'-di-3-propionate)tetrachloridoplatinum(IV) complex under normoxic and hypoxic conditions", volume = "760", pages = "136-144", doi = "10.1016/j.ejphar.2015.04.012" }
Bulatović, M., Kaluderovic, M. R., Mojic, M., Zmejkovski, B., Hey-Hawkins, E., Vidakovic, M., Grdovic, N., Kaluđerović, G. N., Mijatović, S.,& Maksimović-Ivanić, D. D.. (2015). Improved in vitro antitumor potential of (O,O'-Diisobutyl-ethylenediamine-N,N'-di-3-propionate)tetrachloridoplatinum(IV) complex under normoxic and hypoxic conditions. in European Journal of Pharmacology Elsevier., 760, 136-144. https://doi.org/10.1016/j.ejphar.2015.04.012
Bulatović M, Kaluderovic MR, Mojic M, Zmejkovski B, Hey-Hawkins E, Vidakovic M, Grdovic N, Kaluđerović GN, Mijatović S, Maksimović-Ivanić DD. Improved in vitro antitumor potential of (O,O'-Diisobutyl-ethylenediamine-N,N'-di-3-propionate)tetrachloridoplatinum(IV) complex under normoxic and hypoxic conditions. in European Journal of Pharmacology. 2015;760:136-144. doi:10.1016/j.ejphar.2015.04.012 .
Bulatović, Mirna, Kaluderovic, Milena R, Mojic, Marija, Zmejkovski, Bojana, Hey-Hawkins, Evamarie, Vidakovic, Melita, Grdovic, Nevena, Kaluđerović, Goran N., Mijatović, Sanja, Maksimović-Ivanić, Danijela D., "Improved in vitro antitumor potential of (O,O'-Diisobutyl-ethylenediamine-N,N'-di-3-propionate)tetrachloridoplatinum(IV) complex under normoxic and hypoxic conditions" in European Journal of Pharmacology, 760 (2015):136-144, https://doi.org/10.1016/j.ejphar.2015.04.012 . .