Improved in vitro antitumor potential of (O,O'-Diisobutyl-ethylenediamine-N,N'-di-3-propionate)tetrachloridoplatinum(IV) complex under normoxic and hypoxic conditions.
(O,O'-Diisobutyl-ethylenediamine-N,N'-di-3-propionate)tetrachloridoplatinum(IV), [PtCl4(iBu2eddp)], 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(iBu2eddp)] 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.
Department of Immunology, Institute for Biological Research "Sinisa Stankovic", University of Belgrade, Bulevar despota Stefana 142, 11060 Belgrade, Serbia.
Mirna
M
Bulatović
Department of Oral, Maxillary, Facial and Reconstructive Plastic Surgery, University Hospital of Leipzig, 04103 Leipzig, Germany.
Milena R
MR
Kaluđerović
Department of Immunology, Institute for Biological Research "Sinisa Stankovic", University of Belgrade, Bulevar despota Stefana 142, 11060 Belgrade, Serbia.
Marija
M
Mojić
Department of Chemistry, Institute of Chemistry, Technology and Metallurgy, University of Belgrade, Studentski trg 12-16, 11000 Belgrade, Serbia.
Bojana B
BB
Zmejkovski
Institute of Inorganic Chemistry, Leipzig University, Johannisallee 29, D-04103 Leipzig, Germany.
Evamarie
E
Hey-Hawkins
Department of Molecular Biology, Institute for Biological Research "Sinisa Stankovic", University of Belgrade, Bulevar despota Stefana 142, 11060 Belgrade, Serbia.
Melita
M
Vidaković
Department of Molecular Biology, Institute for Biological Research "Sinisa Stankovic", University of Belgrade, Bulevar despota Stefana 142, 11060 Belgrade, Serbia.
Nevena
N
Grdović
Institute of Inorganic Chemistry, Leipzig University, Johannisallee 29, D-04103 Leipzig, Germany; Department of Bioorganic Chemistry, Leibniz Institute of Plant Biochemistry, Weinberg 3, D 06120 Halle (Saale), Germany.
Goran N
GN
Kaluđerović
Department of Immunology, Institute for Biological Research "Sinisa Stankovic", University of Belgrade, Bulevar despota Stefana 142, 11060 Belgrade, Serbia. Electronic address: sanjamama@yahoo.com.
Sanja
S
Mijatović
Department of Immunology, Institute for Biological Research "Sinisa Stankovic", University of Belgrade, Bulevar despota Stefana 142, 11060 Belgrade, Serbia. Electronic address: nelamax@yahoo.com.
Danijela
D
Maksimović-Ivanić
D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology; D015687:Cell Hypoxia / Q000187:drug effects / Q000502:physiology; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects* / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D051379:Mice; D041681:NIH 3T3 Cells; D017671:Platinum Compounds / Q000737:chemistry / Q000494:pharmacology*
D000970:Antineoplastic Agents; D017671:Platinum Compounds; C032741:platinum tetrachloride
ATP depletion; Cisplatin; Cisplatin (PubChem CID: 441203); Hypoxic conditions; Mitochondrial collapse; Oxidative stress; Platinum(IV) complex