Cisplatin Binding Sites on Human Albumin

Ivanov, Andrei I.; Christodoulou, John; Parkinson, John A.; Barnham, Kevin J.; Tucker, Alan; Woodrow, John R.; Sadler, Peter J.

doi:10.1074/jbc.273.24.14721

Cited by 332 publications

(299 citation statements)

References 69 publications

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“…They also bind to many extracellular and intracellular proteins, although they have different binding abilities. 11,12 The formation of protein adducts with platinum-based drugs may be a key event for the tumor killing activities as well as side effects. The chemical structure of cisplatin is quite different from that of carboplatin, although both drugs contain platinum.…”

Section: Discussionmentioning

confidence: 99%

“…Cisplatin contains a platinum atom complexed with two ammonia groups and two chloride residues, and the chloride residue in cisplatin interacts with the sulfur group of the cysteine residue forming a cisplatin-protein complex. 11,13 Cisplatin interacts with caspases by direct binding of the chloride residue in cisplatin with the sulfur group of the cysteine residue in caspases and lead to the inactivation of the caspases due to formation of a complex of cisplatin and caspase. 9 However, the two chlorides in cisplatin have been substituted with 1,1-cyclobutane-dicarboxyl residue in carboplatin (Fig.…”

Section: Discussionmentioning

confidence: 99%

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TRAIL-induced cell death and caspase-8 activation are inhibited by cisplatin but not carboplatin

et al. 2009

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Objective: Platinum (Pt) based drugs including cisplatin and carboplatin are widely used as anticancer drugs in various human cancers. Many studies have shown that chemotherapeutic agents synergistically enhance cell death induced by death ligands. However it has been recently reported that cisplatin may inhibit tumor necrosis factorrelated apoptosis-inducing ligand (TRAIL)-induced cell death through inactivation of caspases. Thus, we investigated whether carboplatin also inhibits TRAIL-induced cell death. Methods: HeLa cells were treated with TRAIL in the presence of cisplatin or carboplatin, and cell death was analyzed using the crystal violet staining method. Caspase activation was checked through detection of Bid cleavage by Western blotting using anti-Bid antibody. Results: Cisplatin inhibits TRAIL-induced cell death in HeLa cells; however, carboplatin enhanced TRAIL-induced cell death. Whereas cisplatin inhibited caspase-8-mediated Bid cleavage, carboplatin had no effect on caspase-8 activity. Conclusion: Although cisplatin and carboplatin are platinum-containing cancer therapeutic agents, they have the opposite effects on TRAIL-induced cell death.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

TRAIL-induced cell death and caspase-8 activation are inhibited by cisplatin but not carboplatin

et al. 2009

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“…Among the latter are bucillamine derivatives, 28) aurothiomalate, 29) auranofin, 30) D-penicillamine, 31,32) captopril, 32,33) ethacrynate, 34) and cisplatin (which also binds to methionine residues). 35) Covalent interaction between thiol-containing drugs and 34 Cys of albumin usually also takes place in vivo. For example, N-acetyl-L-cysteine (and L-cysteine) binds to albumin in plasma; the interaction can be quantitated by a high-performance liquid chromatographic (HPLC) method using hexaiodoplatinate.…”

Section: Ligand Bindingmentioning

confidence: 99%

Practical Aspects of the Ligand-Binding and Enzymatic Properties of Human Serum Albumin.

Kragh‐Hansen

Chuang

Otagiri

2002

Biological & Pharmaceutical Bulletin

910

776

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Recent work with approaches like recombinant mutants and X-ray crystallography has given much new information about the ligand-binding properties of human serum albumin (HSA). The information increases the understanding of this unique transport and depot protein and could give a structural basis for the possible construction of therapeutic agents with altered HSA-binding properties. A tabulation of high-affinity binding sites for both endogenous and exogenous compounds has been made; it could be useful for the above-mentioned purpose, but it could also be of value when trying to predict potential drug interactions at the protein-binding level. Drug displacement is not always a complication to therapy; it can be used to increase the biological effect of a drug. However, due to rebinding at other sites, the increase in the free concentration of a displaced ligand can be less than expected. Drugs and drug metabolites can also interact covalently with HSA; thiol-containing drugs often bind to the single free cysteine residue of HSA, and glucuronidated drugs react irreversibly with other residues of the protein. Reversible binding of ligands is often stereospecific, and therefore immobilized HSA can be used to separate drug isomers. Albumin-containing dialysates are useful for extracorporeal removal of endogenous toxins and in the treatment of drug overdoses. HSA has different types of hydrolytic activities, which also can be stereospecific. The esterase-like property seems especially useful in converting prodrugs to active drugs in plasma.

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“…9 Despite numerous reports on the interaction of cisplatin with albumin, few Pt binding sites have been characterized unambiguously. According to NM R spectroscopic studies, 10 a M et298 S,N-macrochelate is a major cisplatin binding 30 site, and monofunctional adducts involving Cys34 and surface histidine residues are also be formed. Recently, Cys34, M et329, Tyr150 (or Tyr148) and Asp375 (or Glu376) were identified as cisplatin binding sites using multidimensional liquid chromatography coupled with tandem mass spectrometry (LC-…”

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confidence: 99%

The anticancer drug cisplatin can cross-link the interdomain zinc site on human albumin

Luo

et al. 2011

Chem. Commun.

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Cisplatin, cis-[Pt(Cl 2 (NH 3 ) 2 ], can crosslink residues His67 of domain I and His247 of domain II in human albumin, occupying the major binding site for the essential metal zinc on the protein.Cisplatin is a widely used anticancer agent, particularly effective for treating solid tumors such as ovarian, testicular, bladder, head and neck cancers. 1 In vivo, cisplatin is converted to its active forms by aquation, 2 being highly reactive toward biomolecules such as DNA 3 and proteins. 4 Although DNA is probably the crucial target for cisplatin inducing apoptosis and cell death, 5 it is now increasingly recognized that an understanding of its reactions with proteins is very important for understanding its metabolism and side-effects. One day after intravenous administration, 65 to 98% of cisplatin is bound to blood plasma proteins, 6 and most of the Pt (50-61%) from cisplatin added to human blood plasma at physiologically-relevant doses is bound to albumin. 7 Albumin, a 66 kDa single-chain protein consisting of 3 isostructural domains, 8 and present in blood at ca. 0.6 mM, can bind and transport a variety of endogenic and exogenic substances, such as fatty acids, bilirubin, pharmaceuticals and metal ions. 9 Despite numerous reports on the interaction of cisplatin with albumin, few Pt binding sites have been characterized unambiguously. According to NMR spectroscopic studies, 10 a Met298 S,N-macrochelate is a major cisplatin binding site, and monofunctional adducts involving Cys34 and surface histidine residues are also be formed. Recently, Cys34, Met329, Tyr150 (or Tyr148) and Asp375 (or Glu376) were identified as cisplatin binding sites using multidimensional liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS), after

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Cisplatin Binding Sites on Human Albumin

Abstract: Reactions of cisplatin (cis-[

Cited by 332 publications

References 69 publications

TRAIL-induced cell death and caspase-8 activation are inhibited by cisplatin but not carboplatin

TRAIL-induced cell death and caspase-8 activation are inhibited by cisplatin but not carboplatin

Practical Aspects of the Ligand-Binding and Enzymatic Properties of Human Serum Albumin.

The anticancer drug cisplatin can cross-link the interdomain zinc site on human albumin

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