Multiple and Irreversible Binding of cis-Diamminedichloroplatinum(II) to Human Serum Albumin and Its Effect on Warfarin Binding.

Yotsuyanagi, Toshihisa; Ohta, Nobuhiro; Futo, Tomomichi; Ito, Shigekazu; Chen, Danni; Ikeda, Ken

doi:10.1248/cpb.39.3003

Cited by 42 publications

(42 citation statements)

References 1 publication

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“…On the other hand, the CE-ICP-MS experiments presented herein confirmed the possibility of multiple binding of platinum complexes to HSA, involving apparently both specific and nonspecific protein binding centers. One can assume that initially the platinum atom coordinatively binds to the thiol-group of the HSA molecule, namely cysteine-34, which is known as the major site involved in cisplatin interaction [1,5,10,25]. Other chemically favorable platinum binding sites include the methionine-298 residue [7,11].…”

Section: Aminoalcohol Complexesmentioning

confidence: 99%

Platinum metallodrug‐protein binding studies by capillary electrophoresis‐inductively coupled plasma‐mass spectrometry: Characterization of interactions between Pt(II) complexes and human serum albumin

et al. 2004

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Characterizing how platinum metallocomplexes bind to human serum albumin (HSA) is essential in evaluating anticancer drug candidates. Using cisplatin as a reference complex, the application of capillary electrophoresis (CE) to reliably assess drug/HSA interactions was validated. Since this complex is small compared to the size of the protein, the binding response could only be recognized when applying CE coupled to a (platinum) metal-specific mode of detection, namely inductively coupled plasma-mass spectrometry (ICP-MS). This coupling allowed for confirmation of a specific affinity of cisplatin and novel Pt complexes to HSA, measurement of the kinetics of binding reactions, and determination of the number of drug molecules attached to the protein. As the cisplatin/HSA molar ratio increased, the reaction rate became faster with a maximum on the kinetic curve appearing at about 50 h of incubation at 20 times excess of cisplatin. The reaction was characterized as a pseudo-first order reaction with the rate constant k = 0.003 min(-1) at 37 degrees C. When incubated with a 20-fold excess of cisplatin, HSA bound up to 10 mol of Pt per mol of the protein. This is indicative for a strong metal-protein coordination occurring at several HSA sites other than the only protein cysteine residue. Structural analogs of cisplatin, bearing aminoalcohol ligands, showed comparable protein binding reactivity and stoichiometry but a common equilibrium was not reached even after one week of incubation. Also apparent was a two-step mechanism of the binding reaction. Results demonstrated the suitability of CE-ICP-MS as a rapid assay for high-throughput studying of drug/HSA interactions.

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Section: Aminoalcohol Complexesmentioning

confidence: 99%

Platinum metallodrug‐protein binding studies by capillary electrophoresis‐inductively coupled plasma‐mass spectrometry: Characterization of interactions between Pt(II) complexes and human serum albumin

et al. 2004

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“…The use of Opti-MEM is necessary for drug assays because serum contains S-1-P (34) and because cisplatin binds to serum albumin (34,35). Stock solutions were prepared in 3 mmol/L NaCl, 1 mmol/L NaPO 4 (pH 6.5) or in DMSO (not to exceed a final concentration of 0.2% DMSO).…”

Section: Drug Treatment and Cytotoxicity Assaymentioning

confidence: 99%

Sphingosine-1-Phosphate Lyase Regulates Sensitivity of Human Cells to Select Chemotherapy Drugs in a p38-Dependent Manner

Min

Veldhoven

Zhang

et al. 2005

Molecular Cancer Research

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Resistance to cisplatin is a common problem that limits its usefulness in cancer therapy. Molecular genetic studies in the model organism Dictyostelium discoideum have established that modulation of sphingosine kinase or sphingosine-1-phosphate (S-1-P) lyase, by disruption or overexpression, results in altered cellular sensitivity to this widely used drug. Parallel changes in sensitivity were observed for the related compound carboplatin but not for other chemotherapy drugs tested. Sensitivity to cisplatin could also be potentiated pharmacologically with dimethylsphingosine, a sphingosine kinase inhibitor. We now have validated these studies in cultured human cell lines. HEK293 or A549 lung cancer cells expressing human S-1-P lyase (hSPL) show an increase in sensitivity to cisplatin and carboplatin as predicted from the earlier model studies. The hSPL-overexpressing cells were also more sensitive to doxorubicin but not to vincristine or chlorambucil. Studies using inhibitors to specific mitogen-activated protein kinases (MAPK) show that the increased cisplatin sensitivity in the hSPL-overexpressing cells is mediated by p38 and to a lesser extent by c-Jun NH 2 -terminal kinase MAPKs. p38 is not involved in vincristine or chlorambucil cytotoxicity. Measurements of MAPK phosphorylation and enzyme activity as well as small interfering RNA inhibition studies show that the response to the drug is accompanied by up-regulation of p38 and c-Jun NH 2 -terminal kinase and the lack of extracellular signal-regulated kinase up-regulation. These studies confirm an earlier model proposing a mechanism for the drug specificity observed in the studies with D. discoideum and support the idea that the sphingosine kinases and S-1-P lyase are potential targets for improving the efficacy of cisplatin therapy for human tumors. (Mol Cancer Res 2005;3(5):287 -96)

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“…There are three types of sulfur atom in albumin, namely Cys-34 SH, Met thioether, and cystine disulfide. Although previous work on cisplatin-albumin interactions has suggested that platinum can induce cleavage of disulfide bonds, implying binding of platinum to cystine sulfur (35,36), a high excess of platinum and very long incubation times were required to achieve this. Therefore, Cys-34 and Met are the likely sulfur ligands for platinum in the present work.…”

Section: (22) Reaction Of Cis-[pt(mentioning

confidence: 99%

“…Despite numerous studies of cisplatin-albumin binding during the last few decades (7,15,18,19,(33)(34)(35)(36)(37), the precise mechanism of interaction is still poorly understood. Gonias and Pizzo reported that carboxyamidomethylation of the SH group in bovine and human serum albumin resulted in a 4 -5-fold decrease in platinum binding and suggested formation of a single monodentate complex of cisplatin with the free sulfhydryl group (Cys-34) (7,33).…”

mentioning

confidence: 99%

Cisplatin Binding Sites on Human Albumin

Ivanov¹,

Christodoulou²,

Parkinson³

et al. 1998

Journal of Biological Chemistry

335

288

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Multiple and Irreversible Binding of cis-Diamminedichloroplatinum(II) to Human Serum Albumin and Its Effect on Warfarin Binding.

Cited by 42 publications

References 1 publication

Platinum metallodrug‐protein binding studies by capillary electrophoresis‐inductively coupled plasma‐mass spectrometry: Characterization of interactions between Pt(II) complexes and human serum albumin

Platinum metallodrug‐protein binding studies by capillary electrophoresis‐inductively coupled plasma‐mass spectrometry: Characterization of interactions between Pt(II) complexes and human serum albumin

Sphingosine-1-Phosphate Lyase Regulates Sensitivity of Human Cells to Select Chemotherapy Drugs in a p38-Dependent Manner

Cisplatin Binding Sites on Human Albumin

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