Abstract
A series of dichloridoplatinum(II) complexes with selective and high cytotoxicity [IC(90)(96h)≤3 μM] against cisplatin-resistant 1411HP testicular cancer cells were identified. They bear stationary 6-aminomethylnicotinate or 2,4-diaminobutyrate ligands esterified with lipophilic terpenyl residues, i.e., (-)/(+)-menthyl, (+)-cedrenyl, (-)-menthoxypropyl, or with a decyl-tethered 1,1,2-triphenylethene. They accumulated to a larger extent in 1411HP cells than in cells of the cisplatin-sensitive H12.1 germ cell tumour. Their mechanism of apoptosis induction differed from that of cisplatin by being independent of p53 and of caspase-3 activation and by an early loss of the mitochondrial membrane potential. The new complexes are promising candidates for the treatment of cisplatin-resistant testicular tumours.
Copyright © 2011 Elsevier Inc. All rights reserved.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Acetylcysteine / chemistry
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Antineoplastic Agents / chemical synthesis
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Antineoplastic Agents / chemistry
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Antineoplastic Agents / pharmacology*
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Apoptosis / drug effects
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Caspase 3 / metabolism
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Cell Line, Tumor
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Cell Proliferation / drug effects
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Cisplatin / pharmacology*
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Coordination Complexes / chemical synthesis
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Coordination Complexes / chemistry
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Coordination Complexes / pharmacology*
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DNA / chemistry
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DNA Fragmentation
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Drug Resistance, Neoplasm*
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Drug Screening Assays, Antitumor
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Enzyme Activation
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Ethidium / chemistry
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Humans
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Hydrophobic and Hydrophilic Interactions
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Intercalating Agents / chemistry
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Male
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Membrane Potential, Mitochondrial / drug effects
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Platinum*
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Testicular Neoplasms
Substances
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Antineoplastic Agents
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Coordination Complexes
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Intercalating Agents
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Platinum
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DNA
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CASP3 protein, human
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Caspase 3
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Ethidium
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Cisplatin
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Acetylcysteine