A comparison study on RNase A oligomerization induced by cisplatin, carboplatin and oxaliplatin(403 views) Picone D, Donnarumma F, Ferraro G, Gotte G, Fagagnini A, Butera G, Donadelli M, Merlino A
Keywords: Animals, Antineoplastic Agents, Chemistry, Pharmacology, Carboplatin, Cattle, Cisplatin, Organoplatinum Compounds, Protein Binding, Protein Multimerization, Drug Effects, Ribonuclease, Pancreatic, Metabolism, Oxaliplatin, Platinated Ribonucleases, Protein Aggregation, Protein-Metal Interactions, Ribonuclease Oligomers,
Affiliations: *** IBB - CNR ***
Department of Chemical Sciences, University of Naples Federico II, via Cintia, I-80126 Naples, Italy. Electronic address: delia.picone@unina.it., Department of Neuroscience, Biomedicine and Movement, University of Verona, Strada Le Grazie 8, 37134 Verona, Italy., Department of Chemical Sciences, University of Naples Federico II, via Cintia, I-80126 Naples, Italy; Institute of Biostructures and Bioimages, CNR, Via Mezzocannone 16, I-80134 Naples, Italy. Electronic address: antonello.merlino@unina.it.,
References: Not available.
A comparison study on RNase A oligomerization induced by cisplatin, carboplatin and oxaliplatin
Cisplatin (CDDP) can form interprotein cross-links, leading to the formation of platinated oligomers. A dimer, a trimer and higher oligomers of bovine pancreatic ribonuclease (RNase A) obtained upon reaction with CDDP in 1:10 protein to metal ratio at 37 degrees C have been previously characterized. Here, we verify the ability of carboplatin and oxaliplatin to induce RNase A oligomerization under the same experimental conditions. The amount of formed RNase A oligomers was compared with that obtained in the reaction of the protein with CDDP. Among the three anticancer agents, CDDP is the most reactive and the most effective in inhibiting the ribonucleolytic activity of the protein. Oxaliplatin is the least potent oligomerization agent. Biophysical characterizations of structure and stability of platinated dimers formed in the presence of carboplatin and oxaliplatin suggest that they have a similar thermal stability and are more prone to dissociation than the corresponding dimer obtained with CDDP. Oligomers obtained in the presence of carboplatin are the most active. X-ray structures of the monomeric adducts that RNase A forms with the three drugs provide a rational basis to explain the different effects of the three anticancer agents on enzymatic activity and protein aggregation. Although platinated oligomers of RNase A formed upon reaction with CDDP, carboplatin and oxaliplatin retain a residual ribonuclease activity, they do not show cytotoxic action, suggesting that protein aggregation processes induced by Pt-based drugs can represent a collateral drawback, which affects the functional state of protein targets and reduces the efficacy of Pt-based drug treatment.
A comparison study on RNase A oligomerization induced by cisplatin, carboplatin and oxaliplatin
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